Luteinizing hormone (LH) and estradiol suppression and growth in girls with central precocious puberty: is more suppression better? Are pre-injection LH levels useful in monitoring treatment?
BACKGROUND
Girls with central precocious puberty (CPP) are treated with gonadotropin releasing hormone (GnRH) analogues to suppress puberty. Gonadotropin levels are used to monitor treatment, since estradiol is difficult to measure at low levels. The optimal degree of hormonal suppression is still unknown.


OBJECTIVE
We hypothesized that in girls treated for CPP, estradiol levels (by ultrasensitive bioassay) would correlate with the rate of skeletal maturation and linear growth velocity. We asked whether predicted height would improve with greater luteinizing hormone (LH) and estradiol suppression. We also compared pre- and post-injection LH levels for monitoring treatment.


METHODS
Thirty girls with CPP were followed for up to 2 years during treatment with leuprolide acetate depot at a dose of 0.3 mg/kg/28 days. We measured LH and estradiol levels, bone age, and growth velocity every 6 months.


RESULTS
Estradiol levels were suppressed to below the detection limit in three-quarters of the girls and did not correlate with the rate of skeletal maturation or linear growth. Improvement in predicted height correlated significantly with lower pre-injection LH levels. These girls have some of the lowest estradiol and LH levels, best improvement in predicted height, and least amount of bone age advancement published to date. Pre- and post-leuprolide injection LH levels were positively correlated.


CONCLUSIONS
Greater LH suppression may improve height outcome in girls treated for CPP with GnRH analogues. The degree of LH suppression achieved is individualized and not necessarily related to absolute dose. Pre-injection LH levels may be useful for monitoring treatment. Ultrasensitive estradiol levels were very low and usually unmeasurable, affirming the increased suppression at the higher doses of GnRH analogue used in these girls. Further investigation is needed, with longer treatment duration, a range of doses, and ultimately final height. Until such studies are completed, clinicians should be cautious when interpreting pubertal suppression.
Kunz
Gregory J
GJ
Division of Pediatric Endocrinology, University of California, San Diego, CA, USA.
Sherman
Tami Irwin
TI
Klein
Karen Oerter
KO
D001827:Body Height / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D016903:Drug Monitoring / Q000379:methods*; D004958:Estradiol / Q000097:blood*; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000627:therapeutic use*; D006128:Growth / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D007986:Luteinizing Hormone / Q000097:blood*; D011629:Puberty, Precocious / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D011859:Radiography; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D005300:Fertility Agents, Female; D004958:Estradiol; D007986:Luteinizing Hormone; D016729:Leuprolide