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Prolonged pulsatile administration of luteinizing hormone-releasing hormone in prepubertal children: diagnostic and
Insights
Pulsatile luteinizing hormone-releasing hormone (LRH) treatment in children with hypogonadotropic hypogonadism stimulated gonadotropic function, mimicking normal pubertal development and indicating potential therapeutic benefits for endocrine disorders.
Area of Science:
- Pediatric Endocrinology
- Reproductive Endocrinology
- Hormone Therapy
Background:
- Assessing gonadotropic function is crucial for diagnosing and managing pediatric endocrine disorders.
- Pulsatile administration of luteinizing hormone-releasing hormone (LRH) is a key method for stimulating the hypothalamic-pituitary-gonadal axis.
Purpose of the Study:
- To evaluate the effects of pulsatile LRH treatment on gonadotropic function in prepubertal and early pubertal children.
- To assess the recovery of pituitary-gonadal function after LRH withdrawal in different patient groups.
Main Methods:
- Administered pulsatile intravenous LRH (10 mcg every 90 min or 20 mcg/m2 every 96 min) for 7 days to 32 children.
- Conducted LRH stimulation tests (100 mcg/m2 IV) on days 1, 7, and 11/14.
- Measured plasma levels of LH, FSH, estradiol, and testosterone.
Main Results:
- Pulsatile LRH treatment increased gonadotropins in patients with gonadal failure and stimulated steroidogenesis in those with intact function, resembling pubertal development.
- Patients with central endocrine disorders showed varied responses, with subgroup 3a demonstrating intact gonadotropic function indicated by steroid increases.
- After LRH withdrawal, basal gonadotropin levels returned to prepubertal ranges, with a notable LH surge upon re-stimulation.
Conclusions:
- Pulsatile LRH therapy can effectively stimulate gonadotropic function in children with hypogonadotropic hypogonadism.
- The study highlights the utility of LRH testing in differentiating degrees of pituitary-gonadal dysfunction.
- LRH treatment offers a potential therapeutic strategy for inducing pubertal development and restoring reproductive function in select pediatric populations.
Abstract:
In order to test gonadotropic function 30 prepubertal and 2 early pubertal girls and boys were treated with LH-releasing hormone (LRH) in a pulsatile fashion for 7 days. LRH was administered iv either in a dose of 10 micrograms every 90 min or in a dose of 20 micrograms/1.73 m2 every 96 min. On days 1 and 7, just before as well as at the end of LRH treatment, a LRH test (100 micrograms/m2 iv) was performed. In 27 patients a LRH test was repeated 4 (day 11) or 7 days (day 14) after LRH withdrawal as well. Plasma LH, FSH, and estradiol or testosterone levels were estimated during the LRH tests on days 1, 7, and 11/14. The patients were divided into 4 groups: group 1 consisted of 2 girls and 1 boy with gonadal failure, group 2 of 1 girl and 2 boys with intact pituitary and gonadal function, group 3 of 11 girls and 13 boys with various central endocrine disorders, and group 4 of 1 girl and 1 boy with pubertal arrest of unknown origin. In group 1 LRH treatment elicited an increase of both gonadotropins into the castrate range, whereas gonadal steroids did not increase. In group 2 baseline LH as well as the response to LRH increased on day 7. In the boys FSH changed similarly. In the girl baseline FSH increased, but the high FSH response of day 1 decreased. Estradiol and testosterone levels were elevated on day 7. These changes during LRH treatment are similar to those during normal pubertal development. When the LRH test was repeated on day 11/14 basal levels had returned into the prepubertal range and a high response of LH especially was found in all 3 subjects. Patients of group 3 were separated into two subgroups: group 3a, those with, and group 3b, those without an increase of gonadal steroids on day 7 of LRH treatment. Since an increment must be the result of increased gonadotropin stimulation, this probably indicates intact gonadotropic function. Group 3a had a pattern of gonadotropin secretion similar to group 2. In group 3b basal and peak LH levels were lower on day 7 compared to group 3a, whereas FSH levels did not differ. Four or 7 days after LRH discontinuation (day 11/14) basal gonadotropin levels were in the original low range. In the LRH test mean LH peak level of group 3a was 43.7 U/liter, of group 3b 13.1 U/liter (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)