TY - JOUR

T1 - Maternal menopause as a predictor of anti-Mullerian hormone level and antral follicle count in daughters during reproductive age

AU - Bentzen, J G

AU - Forman, J L

AU - Larsen, E C

AU - Pinborg, A

AU - Johannsen, T H

AU - Schmidt, L

AU - Friis-Hansen, L

AU - Andersen, Anders Nyboe

PY - 2013

Y1 - 2013

N2 - STUDY QUESTION: Is the ovarian reserve in a woman at a given age associated with her mother's age at menopause? SUMMARY ANSWER: We demonstrated a significant, positive association between age at maternal menopause and serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) in daughters. The rate of decline in serum-AMH level and AFC is also associated with age at maternal menopause. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The association between menopausal age in mothers and daughters has been established through several epidemiological studies. This paper shows that early maternal menopause is related to an advanced depletion of the ovarian reserve and that late maternal menopause is related to a delayed depletion. STUDY DESIGN AND SIZE: Cross-sectional data were obtained from a prospective cohort study of 863 women. The study comprised 527 participants from this prospective cohort whose mothers' age at natural menopause was known. PARTICIPANTS, SETTING AND METHODS: Participants were recruited from female health care workers aged 20-40 years employed at Copenhagen University Hospital, Rigshospitalet, and were enrolled in the study between September 2008 and February 2010. The response rate was 52.1%. Endocrine and ovarian parameters related to reproductive ageing (AMH and AFC) were assessed by serum AMH analyses and transvaginal ovarian sonography on cycle Day 2-5. Data on reproductive history, including age at natural maternal menopause, were obtained through an internet-based questionnaire. We used an analysis of covariance model with serum-AMH and AFC as outcomes, age as the quantitative predictor and onset of maternal menopause as the categorical predictor, with further adjustments for BMI, use of oral contraceptives, participants' smoking habits and prenatal smoking exposure. MAIN FINDINGS: We found a significant effect of age at maternal menopause on both serum AMH levels (P <0.001) and AFC (P = 0.005). Median serum-AMH concentration declined by 8.6% per year [95% confidence interval (CI): 6.4-10.8%, P <0.001] in the group with early maternal menopausal age (= 45 years), by 6.8% per year (95% CI: 5.0-8.6%, P <0.001) in the group with normal maternal menopausal age (46-54 years) and by 4.2% per year (95% CI: 2.0-6.4%, P <0.001) in the group with late maternal menopausal age (= 55 years). Median AFC declined by 5.8% per year (95% CI: 4.0-7.5%, P <0.001) in the group with early maternal menopausal age (= 45 years), by 4.7% per year (95% CI: 3.3-6.1%, P <0.001) in the group with normal maternal menopausal age (46-54 years) and by 3.2% per year (95% CI: 1.4-4.9%, P <0.001) in the group with late maternal age (= 55 years) at menopause. BIAS, LIMITATIONS AND GENERALIZABILITY: Information on 'age at maternal menopause' was obtained retrospectively and may be prone to recall bias and digit preference. The study population consisted of health care workers, which implies a potential selection bias. Finally, the cross-sectional nature of the data limits the generalizability. STUDY FUNDING/POTENTIAL COMPETING INTERESTS: This study was co-financed by PhD scholarships where funding was covered by the Danish Agency for Science, Technology and Innovation, Copenhagen Graduate School of Health Science (CGSHS) and the Fertility Clinic at Copenhagen University Hospital, Rigshopitalet. No competing interests are declared.

AB - STUDY QUESTION: Is the ovarian reserve in a woman at a given age associated with her mother's age at menopause? SUMMARY ANSWER: We demonstrated a significant, positive association between age at maternal menopause and serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) in daughters. The rate of decline in serum-AMH level and AFC is also associated with age at maternal menopause. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: The association between menopausal age in mothers and daughters has been established through several epidemiological studies. This paper shows that early maternal menopause is related to an advanced depletion of the ovarian reserve and that late maternal menopause is related to a delayed depletion. STUDY DESIGN AND SIZE: Cross-sectional data were obtained from a prospective cohort study of 863 women. The study comprised 527 participants from this prospective cohort whose mothers' age at natural menopause was known. PARTICIPANTS, SETTING AND METHODS: Participants were recruited from female health care workers aged 20-40 years employed at Copenhagen University Hospital, Rigshospitalet, and were enrolled in the study between September 2008 and February 2010. The response rate was 52.1%. Endocrine and ovarian parameters related to reproductive ageing (AMH and AFC) were assessed by serum AMH analyses and transvaginal ovarian sonography on cycle Day 2-5. Data on reproductive history, including age at natural maternal menopause, were obtained through an internet-based questionnaire. We used an analysis of covariance model with serum-AMH and AFC as outcomes, age as the quantitative predictor and onset of maternal menopause as the categorical predictor, with further adjustments for BMI, use of oral contraceptives, participants' smoking habits and prenatal smoking exposure. MAIN FINDINGS: We found a significant effect of age at maternal menopause on both serum AMH levels (P <0.001) and AFC (P = 0.005). Median serum-AMH concentration declined by 8.6% per year [95% confidence interval (CI): 6.4-10.8%, P <0.001] in the group with early maternal menopausal age (= 45 years), by 6.8% per year (95% CI: 5.0-8.6%, P <0.001) in the group with normal maternal menopausal age (46-54 years) and by 4.2% per year (95% CI: 2.0-6.4%, P <0.001) in the group with late maternal menopausal age (= 55 years). Median AFC declined by 5.8% per year (95% CI: 4.0-7.5%, P <0.001) in the group with early maternal menopausal age (= 45 years), by 4.7% per year (95% CI: 3.3-6.1%, P <0.001) in the group with normal maternal menopausal age (46-54 years) and by 3.2% per year (95% CI: 1.4-4.9%, P <0.001) in the group with late maternal age (= 55 years) at menopause. BIAS, LIMITATIONS AND GENERALIZABILITY: Information on 'age at maternal menopause' was obtained retrospectively and may be prone to recall bias and digit preference. The study population consisted of health care workers, which implies a potential selection bias. Finally, the cross-sectional nature of the data limits the generalizability. STUDY FUNDING/POTENTIAL COMPETING INTERESTS: This study was co-financed by PhD scholarships where funding was covered by the Danish Agency for Science, Technology and Innovation, Copenhagen Graduate School of Health Science (CGSHS) and the Fertility Clinic at Copenhagen University Hospital, Rigshopitalet. No competing interests are declared.

U2 - 10.1093/humrep/des356

DO - 10.1093/humrep/des356

M3 - Journal article

C2 - 23136135

VL - 28

SP - 247

EP - 255

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 1

ER -