Ovarian function and reproductive hormone levels in girls with Prader-Willi syndrome: a longitudinal study.
BACKGROUND
The etiology of hypogonadism in girls with Prader-Willi syndrome (PWS) remains uncertain.


OBJECTIVE
The aim of the study was to evaluate gonadal function longitudinally in girls and female adolescents with PWS.


METHODS
We performed a longitudinal assessment of anti-müllerian hormone (AMH), gonadotropins, estradiol (E(2)), inhibin B and A, and pubertal development in girls and female adolescents with PWS.


METHODS
Sixty-one girls participating in the Dutch PWS Cohort study participated in the study. Serum AMH, gonadotropins, E(2), and inhibin B and A levels were compared with reference values.


RESULTS
AMH levels in girls and female adolescents with PWS were comparable to reference levels between 6 months and 22 yr of age. From 10 yr of age, FSH and LH levels increased to above the 5th percentile compared to reference levels. E(2) and inhibin B levels were in the low normal range in the majority, and inhibin A levels were low but detectable in almost half the female adolescents with PWS. The median age at puberty onset was comparable, but the median ages at attaining Tanner M3 (P = 0.05) and M4 (P < 0.0001) were significantly higher in girls with PWS than in healthy references.


CONCLUSIONS
Our study shows that the primordial follicle pool and number of small antral follicles are conserved in girls and female adolescents with PWS. We found no classical hypogonadotropic hypogonadism. However, maturation of follicles and progression of pubertal development are impaired, which might be due to dysregulation of LH secretion. Because these impairments are not absolute, ovulation and thus conception cannot be ruled out in individual female adolescents with PWS.
Dutch Growth Research Foundation, Westzeedijk 106, 3016 AH Rotterdam, The Netherlands. e.siemensma@kindengroei.nl
Elbrich P C
EP
Siemensma
A A E M Janielle
AA
van Alfen-van der Velden
Barto J
BJ
Otten
Joop S E
JS
Laven
Anita C S
AC
Hokken-Koelega
D000293:Adolescent; D000375:Aging / Q000502:physiology; D054304:Anti-Mullerian Hormone / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use; D004967:Estrogens / Q000097:blood*; D005260:Female; D005298:Fertility; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007223:Infant; D007265:Inhibins / Q000097:blood; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D010050:Ovarian Function Tests; D010053:Ovary / Q000503:physiopathology*; D011218:Prader-Willi Syndrome / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D011627:Puberty / Q000502:physiology; D055815:Young Adult
D004967:Estrogens; C422362:inhibin A; C422364:inhibin B; D004958:Estradiol; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone