Urinary beta-FSH subunit concentrations in perimenopausal and postmenopausal women: a biomarker for ovarian reserve.
OBJECTIVE
The purpose of this study was to develop an integrative assessment of pituitary follicle-stimulating hormone (FSH) secretion and to validate these measurements in a population of perimenopausal (PERI) and postmenopausal (POST) women.


METHODS
In this cross-sectional study, 170 POST and 20 PERI women collected first-void morning urine samples and had a single blood sample drawn on the same day. For comparison, 11 midreproductive-aged women had urine samples collected for one menstrual cycle. In addition, one 48.5-year-old woman collected daily urine samples for 4 consecutive years during her menopausal transition. Urine samples were assayed for estrone glucuronide (E1G) and pregnanediol-3-glucuronide (PdG) and were normalized to creatinine. An ELISA assay was developed for measurement of the free beta-FSH subunit in urine.


RESULTS
Mean age (+/- SD) of the PERI and POST women were 48.1 +/- 3.0 and 52.8 +/- 4.1 years, respectively. Mean serum FSH levels were 9.5 +/- 5.8 and 79.3 +/- 32 IU/L (P < 0.001) in the PERI and POST women. Mean urinary beta-FSH/Cr for the PERI were 1.8 +/- 1.2 ng/mg; for the POST, 9.3 +/- 4.5 ng/mg (P < 0.001). Mean estradiol, E1G/Cr, and PdG/Cr levels were also significantly different between the two groups. There was a high correlation between serum FSH and urinary beta-FSH/Cr for the PERI (r = 0.584, P = 0.007) and POST (r = 0.54, P < 0.001), with minimal overlap in the urinary beta-FSH/Cr levels between the PERI and POST groups. A significant correlation between PdG/Cr and urinary beta-FSH/Cr was observed for POST (r = 0.581, P = 0.002). No correlation was seen between urinary beta-FSH/Cr and E1G/Cr or estradiol levels. In the perimenopausal participant, who collected 4 years of daily urine samples, urinary beta-FSH/Cr levels progressively increased during the follicular phase and, by the fourth year, there were persistent, almost tonically high elevations of beta-FSH/Cr in the urine.


CONCLUSIONS
Urinary beta-FSH subunit measurements are a useful marker for monitoring ovarian function during the menopausal transition. Urinary free beta-FSH subunit concentrations reflect pituitary FSH secretion and serve as a biomarker for ovarian reserve.
Liu
James H
JH
Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, OH, USA. James.Liu@uhhs.com
Kao
Lily
L
Rebar
Robert W
RW
Muse
Ken
K
D002979:Climacteric / Q000502:physiology* / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000652:urine*; D006801:Humans; D008183:Luteal Phase / Q000502:physiology*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000502:physiology*; D010050:Ovarian Function Tests; D044384:Ovulation Prediction; D017698:Postmenopause / Q000502:physiology* / Q000652:urine; D012044:Regression Analysis
D005640:Follicle Stimulating Hormone