Girls diagnosed with premature pubarche show an exaggerated ovarian androgen synthesis from the early stages of puberty: evidence from gonadotropin-releasing hormone agonist testing.
OBJECTIVE
To assess the gonadotropin and ovarian steroid responses to the GnRH agonist (GnRH-a) leuprolide acetate (LA) in premature pubarche girls and in Tanner stage- and bone age-matched controls to ascertain whether the ovarian 17-hydroxyprogesterone (17-OHP) hyper-response to GnRH-a challenge present in some subsets of adolescent premature pubarche girls is detectable during puberty and whether these patients have a distinct pattern of pituitary-ovarian maturation.


METHODS
Cross-sectional study.


METHODS
A university teaching hospital.


METHODS
Seventy-six premature pubarche girls (early pubertal [B2; n = 31], midpubertal [B3; n = 15], late pubertal [B4; n = 12], and postmenarcheal [B5; n = 18]) and 45 controls.


METHODS
Gonadotropins and plasma steroid hormones (17-OHP, 17-OH-pregnenolone [17-Preg], androstenedione [A], T, DHEA, DHEAS, E2, and cortisol) were measured before and 3 and 24 hours, respectively, after LA challenge (500 micrograms SC).


METHODS
Ovarian-steroidogenic responses to GnRH-a challenge.


RESULTS
Luteinizing hormone responsiveness increased significantly during puberty in all subjects whereas FSH levels changed less consistently. Peak E2 levels differed among pubertal stages and were significantly higher in premature pubarche girls than in controls at B4 and at B5. Both peak and incremental increases of 17-Preg and DHEA throughout puberty and of 17-OHP and A at B4 were significantly higher in premature pubarche girls than in controls. This pattern of ovarian-steroidogenic response was most evident during midpuberty and late puberty and resembled the adrenal hyper-response to ACTH of exaggerated adrenarche, suggestive of increased ovarian activity of both the 17 alpha-hydroxylase and the 17,20 lyase functions of cytochrome P450c17 alpha.


CONCLUSIONS
Pubertal girls with a history of premature pubarche show a distinct pattern of ovarian maturation characterized by an exaggerated ovarian androgen synthesis throughout puberty.
Ibáñez
L
L
Hospital Materno-Infantil Vall d'Hebron, Autonomous University of Barcelona, Spain.
Potau
N
N
Zampolli
M
M
Street
M E
ME
Carrascosa
A
A
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000097:blood; D002648:Child; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000378:metabolism*; D011629:Puberty, Precocious / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D006907:17-alpha-Hydroxypregnenolone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide