The Relationship Between Variation in Size of the Primordial Follicle Pool and Age at Natural Menopause.
BACKGROUND
Menopause has been hypothesized to occur when the nongrowing follicle (NGF) number falls below a critical threshold. Age at natural menopause can be predicted using NGF numbers and this threshold. These predictions support the use of ovarian reserve tests, reflective of the ovarian follicle pool, in menopause forecasting.


OBJECTIVE
The objective of the study was to investigate the hypothesis that age-specific NGF numbers reflect age at natural menopause.


METHODS
Histologically derived NGF numbers obtained from published literature (n = 218) and distribution of menopausal ages derived from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort (n = 4037) were combined.


METHODS
NGF data were from single ovaries that had been obtained postnatally for various reasons, such as elective surgery or autopsy. From the Prospect-EPIC cohort, women aged 58 years and older with a known age at natural menopause were selected.


METHODS
There were no interventions.


METHODS
Conformity between observed age at menopause in the Prospect-EPIC cohort and NGF-predicted age at menopause from a model for age-related NGF decline constructed using a robust regression analysis. A critical threshold for NGF number was estimated by comparing the probability distribution of the age at which the NGF numbers fall below this threshold with the observed distribution of age at natural menopause from the Prospect-EPIC cohort.


RESULTS
The distributions of observed age at natural menopause and predicted age at natural menopause showed close conformity.


CONCLUSIONS
The close conformity observed between NGF-predicted and actual age at natural menopause supports the hypothesis that that the size of the primordial follicle pool is an important determinant for the length of the individual ovarian life span and supports the concept of menopause prediction using ovarian reserve tests, such as anti-Müllerian hormone and antral follicle count, as derivatives of the true ovarian reserve.
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
M
M
Depmann
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
M J
MJ
Faddy
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
Y T
YT
van der Schouw
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
P H M
PH
Peeters
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
S L
SL
Broer
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
T W
TW
Kelsey
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
S M
SM
Nelson
Department of Reproductive Medicine and Gynecology (M.D., S.L.B., F.J.M.B.), Julius Center for Health Sciences and Primary Care (Y.T.v.d.S., P.H.M.P.), University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; School of Mathematical Sciences (M.J.F.), Queensland University of Technology, Brisbane, Queensland 4001, Australia; School of Computer Science (T.W.K.), University of St Andrews, St Andrews KY16 9AJ, Scotland, United Kingdom; and School of Medicine (S.M.N.), University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom.
F J M
FJ
Broekmans
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000502:physiology; D048429:Cell Size; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000166:cytology*; D065851:Ovarian Reserve / Q000502:physiology*; D010053:Ovary / Q000166:cytology*; D011247:Pregnancy; D055815:Young Adult