Evidence of early ovarian aging in fragile X premutation carriers.
Up to 28% of female fragile X premutation carriers develop premature ovarian failure. To test the hypothesis that fragile X premutation carriers with ovulatory menstrual cycles exhibit hormone changes characteristic of early ovarian aging, 11 regularly cycling fragile X premutation carriers, 24-41 yr old (34.5 +/- 5.7 yr, mean +/- sd), drew daily blood samples across one menstrual cycle. LH, FSH, estradiol, progesterone (P4), inhibin A, and inhibin B levels were compared with levels in 22 age-matched, regularly cycling women, 23-41 yr old (34.6 +/- 5.8 yr), at each cycle stage. Total cycle (26.1 +/- 1.0 vs. 28.2 +/- 0.4 d; P < 0.05) and follicular phase length (12.9 +/- 0.8 vs. 14.5 +/- 0.4 d; P < 0.05) were decreased in fragile X premutation carriers compared with age-matched controls, whereas luteal phase length was similar (13.2 +/- 0.5 vs. 13.7 +/- 0.3 d; P = not significant). FSH was elevated across the follicular (21.9 +/- 3.5 vs. 11.2 +/- 0.5 IU/liter; P < 0.001) and luteal phases (14.6 +/- 3.9 vs. 7.9 +/- 0.5 IU/liter; P < 0.05) in fragile X premutation carriers compared with age-matched controls. Inhibin B in the follicular phase (77 +/- 11 vs. 104 +/- 6 pg/ml; P < 0.05) and inhibin A (3.4 +/- 0.7 vs. 5.8 +/- 0.5 IU/ml; P < 0.01) and P4 [7.3 +/- 1.0 vs. 10.1 +/- 0.7 ng/ml (23.2 +/- 3.0 vs. 32.1 +/- 2.3 nmol/liter); P < 0.05] in the luteal phase were decreased in fragile X premutation carriers compared with age-matched controls, whereas there was no difference in estradiol or LH. In summary, despite regular ovulatory cycles, FSH was increased in fragile X premutation carriers compared with age-matched controls. The increased FSH was accompanied by decreased inhibin B in the follicular phase and inhibin A and P4 in the luteal phase. These hormonal changes suggest that fragile X premutation carriers exhibit early ovarian aging despite regular menstrual cycles. Early ovarian aging in fragile X premutation carriers likely results from decreased follicle number and function, as reflected by lower inhibin B, inhibin A, and P4 levels.
Welt
C K
CK
Reproductive Endocrine, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA. cwelt@partners.org
Smith
P C
PC
Taylor
A E
AE
D000328:Adult; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D007265:Inhibins / Q000097:blood; D008597:Menstrual Cycle; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis; D010053:Ovary / Q000503:physiopathology*; D016601:RNA-Binding Proteins / Q000032:analysis; D018911:Trinucleotide Repeats
D004958:Estradiol; D005640:Follicle Stimulating Hormone; D051860:Fragile X Messenger Ribonucleoprotein 1; D007265:Inhibins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C422364:inhibin B