Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan.

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.(1) We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data. We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.

Familial central precocious puberty suggests autosomal dominant inheritance.

The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 +/- 1.96 vs. 12.66 +/- 1.18 yr; P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young siblings) assuming incomplete penetrance and 0.58 (0.65 after exclusion of young siblings) assuming complete ascertainment. These results suggest autosomal dominant transmission with incomplete, sex-dependent penetrance.

Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys.

OBJECTIVES: The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH-a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests. PATIENTS, METHODS AND DESIGN: The study sample included 32 prepubertal boys aged 14 years or older. Thirteen entered spontaneous puberty within 1 year of referral (group A) and 19 remained prepubertal (group B). All underwent the GnRH test (Relefact, Hoechst AG, 0.1 mg/m2 i.v. in one bolus), GnRH-a test (Decapeptyl, Ferring GmbH, 0.1 mg/m2 s.c.) and hCG stimulation (Chorigon, Teva, 1500 units i.m. on three alternate days) at 1-week intervals. All tests were performed at referral at 0800 h. Blood samples were collected before testing and at 30 and 60 min (GnRH test) or 4 h (GnRH-a) for LH and FSH determination, and before testing and at 4 h (GnRH-a) or on the seventh day (hCG) after stimulation for serum testosterone measurement. RESULTS: The LH response to GnRH-a and the testosterone response to hCG stimulation were significantly higher in group A (LH, mean +/- SD 20.4 +/- 7.5 mIU/ml, range 10.8-32.6; testosterone, mean +/- SD 18.0 +/- 5.9 nmol/l, range 9.4-26, P < 0.0001) than in group B (LH, mean +/- SD 2.3 +/- 2.0 mIU/ml, range 0.7-6.9; testosterone, mean +/- SD 1.0 +/- 0.7 nmol/l, range 0.7-3.2), with no overlap between the groups. The cut-off for the LH response to GnRH-a was 8.0 mIU/ml, and for the testosterone response to hCG, 8 nmol/l. There were also significant differences between the groups in mean basal serum LH and FSH (LH, 1.1 +/- 0.5 vs. 0.6 +/- 0.2 mIU/ml, P < 0.05; FSH, 2.2 +/- 2.0 vs. 0.4 +/- 0.3 mIU/ml, P < 0.02) and their response to GnRH (LH, 11.4 +/- 4.4 vs. 2.7 +/- 1.1 mIU/ml, P < 0.0001; FSH, 5.1 +/- 3.4 vs. 2.5 +/- 2.4 mIU/ml, P < 0.0001), and mean serum testosterone level at 4 h after GnRH-a administration (1.9 +/- 1.0 vs. 0.9 +/- 0.4 nmol/l, P = 0.002), but all showed a great overlap in range. Mean age, testicular volume and basal serum testosterone levels were similar in the two groups at referral. One year later, the testicular volume of group A (5.0-12.0 ml) was significantly larger than that of group B (1.0-3.0 ml, P < 0.0001), which remained unchanged on re-examination 3.0 +/- 0.5 years later. CONCLUSIONS: The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.