Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study.
BACKGROUND
The aim of this study was to evaluate the effect of a single dose of leuprolide acetate on gonadotrophin and gonadal steroid secretion in brothers of women with polycystic ovary syndrome (PCOS), in order to assess P450c17alpha activity. An oral glucose tolerance test (OGTT) and a lipid profile were also performed.


METHODS
Twenty-two unrelated brothers of women with PCOS (PCOS(b)) and 14 brothers of normal cycling women (C(b)), matched for age, underwent a leuprolide acetate test (10 microg/kg s.c.) and an OGTT with measurement of circulating concentrations of gonadotrophins, steroid hormones, glucose, insulin and lipids.


RESULTS
Clinical and basal hormonal parameters were similar in both groups. After leuprolide administration, PCOS(b) exhibited a significant increase of 17alpha-hydroxyprogesterone (17-OHP) compared to C(b) (P<0.05). However, only 45% of PCOS(b) showed a supranormal increase of 17-OHP (2 SD above the respective control group mean values, P<0.003) with a normal gonadotrophin response (group 1). The other 55% of the PCOS(b) exhibited a normal 17-OHP response to the analogue (group 2). However, in group 2, basal steroid concentrations did not show a uniform pattern: six of the PCOS(b) exhibited high basal androstenedione (2 SD above the respective control group mean values), three were very similar to C(b), and the other three presented lower basal testosterone concentrations (2 SD below the respective control group mean values) than those observed in C(b).


CONCLUSIONS
This study shows that different responses to leuprolide in PCOS brothers make evident the heterogeneity of this syndrome in which P450c17alpha activity could be involved.
Petermann
T Sir
TS
Laboratory of Endocrinology, Department of Medicine, San Juan de Dios Hospital, School of Medicine, University of Chile, Chile. tsir@med.uchile.cl
Cartes
A
A
Maliqueo
M
M
Vantman
D
D
Gutiérrez
C
C
Toloza
H
H
Echiburú
B
B
Recabarren
S E
SE
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000328:Adult; D000505:Alopecia; D000735:Androstenedione / Q000097:blood; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D018740:Genetic Heterogeneity; D005951:Glucose Tolerance Test; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D012016:Reference Values; D035781:Siblings; D013739:Testosterone / Q000097:blood
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide