Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age

J. G. Bentzen, A. Pinborg, E. C. Larsen, Elisabeth Wreford Andersen, T. H. Johannsen, L. Friis-Hansen, A. Nyboe Andersen

Research output: Contribution to journalConference abstract in journalResearchpeer-review

Abstract

Introduction: Maternal age at menopause is hypothesized to influence daughters’ ovarian reserve. We explored this hypothesis by assessing the ovarian reserve through anti-Müllerian hormone levels (AMH) and antral follicle count (AFC) in healthy women of reproductive age.

Material and Methods: A prospective cohort study of 863 healthy female healthcare workers aged 20–40 years employed at Copenhagen University Hospital. We analysed a subpopulation of women (n = 528) whose mother’s age at natural menopause was known. Data were obtained on menstrual cycle, smoking habits including prenatal smoking exposure, reproductive history, and mother’s age at menopause. On menstrual cycle Day 2–6 plasma hormone levels were assessed and a transvaginal sonography was performed measuring AFC. Women taken a combined oral contraceptive were studied on menstrual cycle Day 2–6 (during withdrawal bleeding). Pregnant women (n = 67) were excluded. Multiple linear regression analyses were performed to investigate the effect of participants’ age and their mother’s age at menopause on AMH levels and AFC with adjustment for use of oral contraceptives, follicle-stimulating hormone levels, participants’ smoking habits and mothers’ smoking habits during pregnancy. All mean values are reported as adjusted with 95%CI.

Results: Participants were stratified into three age groups: 20.0–29.9 years, 30.0–34.9 years and 35.0–39.9 years. Age at maternal menopause was normally distributed (mean age 50.2 years). Based on the age at maternal menopause three groups were defined according to the 10th and the 90th percentile: early maternal menopause (≤ 45 years) (n = 68), normal maternal menopause (46–54 years) (n = 383) and late maternal menopause ( ≥ 55 years) (n = 77). In the group with normal maternal menopause the AMH levels and AFC differed significantly according to participants’ age. Participants aged 20.0–29.9 years, 30.0–34.9 years, and 35.0–39.9 years had adjusted mean AMH levels of 16.6 pmol/L [95%CI 13.5–20.6], 12.4 [10.2–15.1], and 8.5 [7.0–10.5], respectively (p < 0.001) and adjusted mean AFC values of 17.1 [95%CI 14.5–20.2], 14.7 [12.6–17.1], and 10.3 [8.7–12.1], respectively (p < 0.001). In the group with early maternal menopause a significant decrease in AMH level (p < 0.001) and AFC (p = 0.002) was shown when comparing participants aged 20.0–29.9 years with participants aged 30.0–34.9 years. The corresponding adjusted mean AMH levels were 18.6 pmol/L [95%CI 12.4–27.9], 9.2 [6.6–12.7], and 6.9 [5.0–9.4], respectively and the adjusted mean AFC values were 17.7 [95%CI 12.9–24.3], 11.4 [8.8–14.7], and 9.9 [7.7–12.7], respectively. In the group with late maternal menopause no significant differences were seen in AMH levels (p = 0.22) and AFC (p = 0.76) across the three age groups. The corresponding adjusted mean AMH levels were 14.4 pmol/L [95%CI 9.2–22.5], 12.2 [9.1–16.3], and 15.4 [11.1–21.4], respectively, and the adjusted mean AFC values were 14.3 [95%CI 10.0–20.2], 14.4 [11.5–18.2], and 15.1 [11.7–19.5], respectively. Crude and adjusted analyses showed consistent effects of age at maternal menopause on AMH and AFC levels in the daughters. Participants’ smoking habits and mothers’ smoking habits during pregnancy did not infuence AMH levels or AFC.

Conclusions: These cross-sectional data showed that women whose mothers entered menopause at a normal age had the expected decline in ovarian reserve with increasing age. However, women whose mothers entered menopause before the age of 45 years had an early, marked decrease in ovarian reserve. In women whose mothers entered menopause after the age of 55 years, the plasma levels of AMH and the antral follicle count remained stable at least up to 40 years of age, indicating that the ovarian follicular depletion may be postponed in these women. Our data support the hypothesis that hereditary factors have a major impact on the ovarian follicular depletion rate.
Original languageEnglish
Article numberO-010
JournalHuman Reproduction
Volume26
Issue numberSuppl. 1
Pages (from-to)I4-I5
ISSN0268-1161
DOIs
Publication statusPublished - 2011
Externally publishedYes
Event27th Annual Meeting of the European Society of Human Reproduction and Embryology - Stockholm, Sweden
Duration: 3 Jul 20116 Jul 2011
Conference number: 27

Conference

Conference27th Annual Meeting of the European Society of Human Reproduction and Embryology
Number27
CountrySweden
CityStockholm
Period03/07/201106/07/2011

Keywords

  • follicle count
  • hereditary factor
  • late maternal menopause
  • menstrual cycle
  • ovarian follicular depletion rate
  • ovarian reserve
  • pregnancy
  • reproductive age
  • smoking habit
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common adult, middle age female
  • anti-Muellerian hormone AMH 80497-65-0
  • contraceptive drug contraceptive-drug oral administration
  • follicle-stimulating hormone 9002-68-0
  • 00520, General biology - Symposia, transactions and proceedings
  • 10060, Biochemistry studies - General
  • 12512, Pathology - Therapy
  • 16504, Reproductive system - Physiology and biochemistry
  • 22005, Pharmacology - Clinical pharmacology
  • 22028, Pharmacology - Reproductive system and implantation studies
  • Reproduction
  • antral follicle reproductive system
  • transvaginal sonography laboratory techniques, diagnostic techniques, clinical techniques, imaging and microscopy techniques
  • Biochemistry and Molecular Biophysics
  • Reproductive System

Cite this

Bentzen, J. G., Pinborg, A., Larsen, E. C., Andersen, E. W., Johannsen, T. H., Friis-Hansen, L., & Andersen, A. N. (2011). Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age. Human Reproduction, 26(Suppl. 1), I4-I5. [O-010]. https://doi.org/10.1093/humrep/26.s1.3
Bentzen, J. G. ; Pinborg, A. ; Larsen, E. C. ; Andersen, Elisabeth Wreford ; Johannsen, T. H. ; Friis-Hansen, L. ; Andersen, A. Nyboe. / Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age. In: Human Reproduction. 2011 ; Vol. 26, No. Suppl. 1. pp. I4-I5.
@article{9ecf38bd4ad4409abf11a1c865ca3bec,
title = "Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age",
abstract = "Introduction: Maternal age at menopause is hypothesized to influence daughters’ ovarian reserve. We explored this hypothesis by assessing the ovarian reserve through anti-M{\"u}llerian hormone levels (AMH) and antral follicle count (AFC) in healthy women of reproductive age.Material and Methods: A prospective cohort study of 863 healthy female healthcare workers aged 20–40 years employed at Copenhagen University Hospital. We analysed a subpopulation of women (n = 528) whose mother’s age at natural menopause was known. Data were obtained on menstrual cycle, smoking habits including prenatal smoking exposure, reproductive history, and mother’s age at menopause. On menstrual cycle Day 2–6 plasma hormone levels were assessed and a transvaginal sonography was performed measuring AFC. Women taken a combined oral contraceptive were studied on menstrual cycle Day 2–6 (during withdrawal bleeding). Pregnant women (n = 67) were excluded. Multiple linear regression analyses were performed to investigate the effect of participants’ age and their mother’s age at menopause on AMH levels and AFC with adjustment for use of oral contraceptives, follicle-stimulating hormone levels, participants’ smoking habits and mothers’ smoking habits during pregnancy. All mean values are reported as adjusted with 95{\%}CI.Results: Participants were stratified into three age groups: 20.0–29.9 years, 30.0–34.9 years and 35.0–39.9 years. Age at maternal menopause was normally distributed (mean age 50.2 years). Based on the age at maternal menopause three groups were defined according to the 10th and the 90th percentile: early maternal menopause (≤ 45 years) (n = 68), normal maternal menopause (46–54 years) (n = 383) and late maternal menopause ( ≥ 55 years) (n = 77). In the group with normal maternal menopause the AMH levels and AFC differed significantly according to participants’ age. Participants aged 20.0–29.9 years, 30.0–34.9 years, and 35.0–39.9 years had adjusted mean AMH levels of 16.6 pmol/L [95{\%}CI 13.5–20.6], 12.4 [10.2–15.1], and 8.5 [7.0–10.5], respectively (p < 0.001) and adjusted mean AFC values of 17.1 [95{\%}CI 14.5–20.2], 14.7 [12.6–17.1], and 10.3 [8.7–12.1], respectively (p < 0.001). In the group with early maternal menopause a significant decrease in AMH level (p < 0.001) and AFC (p = 0.002) was shown when comparing participants aged 20.0–29.9 years with participants aged 30.0–34.9 years. The corresponding adjusted mean AMH levels were 18.6 pmol/L [95{\%}CI 12.4–27.9], 9.2 [6.6–12.7], and 6.9 [5.0–9.4], respectively and the adjusted mean AFC values were 17.7 [95{\%}CI 12.9–24.3], 11.4 [8.8–14.7], and 9.9 [7.7–12.7], respectively. In the group with late maternal menopause no significant differences were seen in AMH levels (p = 0.22) and AFC (p = 0.76) across the three age groups. The corresponding adjusted mean AMH levels were 14.4 pmol/L [95{\%}CI 9.2–22.5], 12.2 [9.1–16.3], and 15.4 [11.1–21.4], respectively, and the adjusted mean AFC values were 14.3 [95{\%}CI 10.0–20.2], 14.4 [11.5–18.2], and 15.1 [11.7–19.5], respectively. Crude and adjusted analyses showed consistent effects of age at maternal menopause on AMH and AFC levels in the daughters. Participants’ smoking habits and mothers’ smoking habits during pregnancy did not infuence AMH levels or AFC.Conclusions: These cross-sectional data showed that women whose mothers entered menopause at a normal age had the expected decline in ovarian reserve with increasing age. However, women whose mothers entered menopause before the age of 45 years had an early, marked decrease in ovarian reserve. In women whose mothers entered menopause after the age of 55 years, the plasma levels of AMH and the antral follicle count remained stable at least up to 40 years of age, indicating that the ovarian follicular depletion may be postponed in these women. Our data support the hypothesis that hereditary factors have a major impact on the ovarian follicular depletion rate.",
keywords = "follicle count, hereditary factor, late maternal menopause, menstrual cycle, ovarian follicular depletion rate, ovarian reserve, pregnancy, reproductive age, smoking habit, Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common adult, middle age female, anti-Muellerian hormone AMH 80497-65-0, contraceptive drug contraceptive-drug oral administration, follicle-stimulating hormone 9002-68-0, 00520, General biology - Symposia, transactions and proceedings, 10060, Biochemistry studies - General, 12512, Pathology - Therapy, 16504, Reproductive system - Physiology and biochemistry, 22005, Pharmacology - Clinical pharmacology, 22028, Pharmacology - Reproductive system and implantation studies, Reproduction, antral follicle reproductive system, transvaginal sonography laboratory techniques, diagnostic techniques, clinical techniques, imaging and microscopy techniques, Biochemistry and Molecular Biophysics, Reproductive System",
author = "Bentzen, {J. G.} and A. Pinborg and Larsen, {E. C.} and Andersen, {Elisabeth Wreford} and Johannsen, {T. H.} and L. Friis-Hansen and Andersen, {A. Nyboe}",
year = "2011",
doi = "10.1093/humrep/26.s1.3",
language = "English",
volume = "26",
pages = "I4--I5",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "Suppl. 1",

}

Bentzen, JG, Pinborg, A, Larsen, EC, Andersen, EW, Johannsen, TH, Friis-Hansen, L & Andersen, AN 2011, 'Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age', Human Reproduction, vol. 26, no. Suppl. 1, O-010, pp. I4-I5. https://doi.org/10.1093/humrep/26.s1.3

Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age. / Bentzen, J. G.; Pinborg, A.; Larsen, E. C.; Andersen, Elisabeth Wreford; Johannsen, T. H.; Friis-Hansen, L.; Andersen, A. Nyboe.

In: Human Reproduction, Vol. 26, No. Suppl. 1, O-010, 2011, p. I4-I5.

Research output: Contribution to journalConference abstract in journalResearchpeer-review

TY - ABST

T1 - Late maternal menopause is associated with stable anti-Mullerian hormone levels and antral follicle count in daughters during reproductive age

AU - Bentzen, J. G.

AU - Pinborg, A.

AU - Larsen, E. C.

AU - Andersen, Elisabeth Wreford

AU - Johannsen, T. H.

AU - Friis-Hansen, L.

AU - Andersen, A. Nyboe

PY - 2011

Y1 - 2011

N2 - Introduction: Maternal age at menopause is hypothesized to influence daughters’ ovarian reserve. We explored this hypothesis by assessing the ovarian reserve through anti-Müllerian hormone levels (AMH) and antral follicle count (AFC) in healthy women of reproductive age.Material and Methods: A prospective cohort study of 863 healthy female healthcare workers aged 20–40 years employed at Copenhagen University Hospital. We analysed a subpopulation of women (n = 528) whose mother’s age at natural menopause was known. Data were obtained on menstrual cycle, smoking habits including prenatal smoking exposure, reproductive history, and mother’s age at menopause. On menstrual cycle Day 2–6 plasma hormone levels were assessed and a transvaginal sonography was performed measuring AFC. Women taken a combined oral contraceptive were studied on menstrual cycle Day 2–6 (during withdrawal bleeding). Pregnant women (n = 67) were excluded. Multiple linear regression analyses were performed to investigate the effect of participants’ age and their mother’s age at menopause on AMH levels and AFC with adjustment for use of oral contraceptives, follicle-stimulating hormone levels, participants’ smoking habits and mothers’ smoking habits during pregnancy. All mean values are reported as adjusted with 95%CI.Results: Participants were stratified into three age groups: 20.0–29.9 years, 30.0–34.9 years and 35.0–39.9 years. Age at maternal menopause was normally distributed (mean age 50.2 years). Based on the age at maternal menopause three groups were defined according to the 10th and the 90th percentile: early maternal menopause (≤ 45 years) (n = 68), normal maternal menopause (46–54 years) (n = 383) and late maternal menopause ( ≥ 55 years) (n = 77). In the group with normal maternal menopause the AMH levels and AFC differed significantly according to participants’ age. Participants aged 20.0–29.9 years, 30.0–34.9 years, and 35.0–39.9 years had adjusted mean AMH levels of 16.6 pmol/L [95%CI 13.5–20.6], 12.4 [10.2–15.1], and 8.5 [7.0–10.5], respectively (p < 0.001) and adjusted mean AFC values of 17.1 [95%CI 14.5–20.2], 14.7 [12.6–17.1], and 10.3 [8.7–12.1], respectively (p < 0.001). In the group with early maternal menopause a significant decrease in AMH level (p < 0.001) and AFC (p = 0.002) was shown when comparing participants aged 20.0–29.9 years with participants aged 30.0–34.9 years. The corresponding adjusted mean AMH levels were 18.6 pmol/L [95%CI 12.4–27.9], 9.2 [6.6–12.7], and 6.9 [5.0–9.4], respectively and the adjusted mean AFC values were 17.7 [95%CI 12.9–24.3], 11.4 [8.8–14.7], and 9.9 [7.7–12.7], respectively. In the group with late maternal menopause no significant differences were seen in AMH levels (p = 0.22) and AFC (p = 0.76) across the three age groups. The corresponding adjusted mean AMH levels were 14.4 pmol/L [95%CI 9.2–22.5], 12.2 [9.1–16.3], and 15.4 [11.1–21.4], respectively, and the adjusted mean AFC values were 14.3 [95%CI 10.0–20.2], 14.4 [11.5–18.2], and 15.1 [11.7–19.5], respectively. Crude and adjusted analyses showed consistent effects of age at maternal menopause on AMH and AFC levels in the daughters. Participants’ smoking habits and mothers’ smoking habits during pregnancy did not infuence AMH levels or AFC.Conclusions: These cross-sectional data showed that women whose mothers entered menopause at a normal age had the expected decline in ovarian reserve with increasing age. However, women whose mothers entered menopause before the age of 45 years had an early, marked decrease in ovarian reserve. In women whose mothers entered menopause after the age of 55 years, the plasma levels of AMH and the antral follicle count remained stable at least up to 40 years of age, indicating that the ovarian follicular depletion may be postponed in these women. Our data support the hypothesis that hereditary factors have a major impact on the ovarian follicular depletion rate.

AB - Introduction: Maternal age at menopause is hypothesized to influence daughters’ ovarian reserve. We explored this hypothesis by assessing the ovarian reserve through anti-Müllerian hormone levels (AMH) and antral follicle count (AFC) in healthy women of reproductive age.Material and Methods: A prospective cohort study of 863 healthy female healthcare workers aged 20–40 years employed at Copenhagen University Hospital. We analysed a subpopulation of women (n = 528) whose mother’s age at natural menopause was known. Data were obtained on menstrual cycle, smoking habits including prenatal smoking exposure, reproductive history, and mother’s age at menopause. On menstrual cycle Day 2–6 plasma hormone levels were assessed and a transvaginal sonography was performed measuring AFC. Women taken a combined oral contraceptive were studied on menstrual cycle Day 2–6 (during withdrawal bleeding). Pregnant women (n = 67) were excluded. Multiple linear regression analyses were performed to investigate the effect of participants’ age and their mother’s age at menopause on AMH levels and AFC with adjustment for use of oral contraceptives, follicle-stimulating hormone levels, participants’ smoking habits and mothers’ smoking habits during pregnancy. All mean values are reported as adjusted with 95%CI.Results: Participants were stratified into three age groups: 20.0–29.9 years, 30.0–34.9 years and 35.0–39.9 years. Age at maternal menopause was normally distributed (mean age 50.2 years). Based on the age at maternal menopause three groups were defined according to the 10th and the 90th percentile: early maternal menopause (≤ 45 years) (n = 68), normal maternal menopause (46–54 years) (n = 383) and late maternal menopause ( ≥ 55 years) (n = 77). In the group with normal maternal menopause the AMH levels and AFC differed significantly according to participants’ age. Participants aged 20.0–29.9 years, 30.0–34.9 years, and 35.0–39.9 years had adjusted mean AMH levels of 16.6 pmol/L [95%CI 13.5–20.6], 12.4 [10.2–15.1], and 8.5 [7.0–10.5], respectively (p < 0.001) and adjusted mean AFC values of 17.1 [95%CI 14.5–20.2], 14.7 [12.6–17.1], and 10.3 [8.7–12.1], respectively (p < 0.001). In the group with early maternal menopause a significant decrease in AMH level (p < 0.001) and AFC (p = 0.002) was shown when comparing participants aged 20.0–29.9 years with participants aged 30.0–34.9 years. The corresponding adjusted mean AMH levels were 18.6 pmol/L [95%CI 12.4–27.9], 9.2 [6.6–12.7], and 6.9 [5.0–9.4], respectively and the adjusted mean AFC values were 17.7 [95%CI 12.9–24.3], 11.4 [8.8–14.7], and 9.9 [7.7–12.7], respectively. In the group with late maternal menopause no significant differences were seen in AMH levels (p = 0.22) and AFC (p = 0.76) across the three age groups. The corresponding adjusted mean AMH levels were 14.4 pmol/L [95%CI 9.2–22.5], 12.2 [9.1–16.3], and 15.4 [11.1–21.4], respectively, and the adjusted mean AFC values were 14.3 [95%CI 10.0–20.2], 14.4 [11.5–18.2], and 15.1 [11.7–19.5], respectively. Crude and adjusted analyses showed consistent effects of age at maternal menopause on AMH and AFC levels in the daughters. Participants’ smoking habits and mothers’ smoking habits during pregnancy did not infuence AMH levels or AFC.Conclusions: These cross-sectional data showed that women whose mothers entered menopause at a normal age had the expected decline in ovarian reserve with increasing age. However, women whose mothers entered menopause before the age of 45 years had an early, marked decrease in ovarian reserve. In women whose mothers entered menopause after the age of 55 years, the plasma levels of AMH and the antral follicle count remained stable at least up to 40 years of age, indicating that the ovarian follicular depletion may be postponed in these women. Our data support the hypothesis that hereditary factors have a major impact on the ovarian follicular depletion rate.

KW - follicle count

KW - hereditary factor

KW - late maternal menopause

KW - menstrual cycle

KW - ovarian follicular depletion rate

KW - ovarian reserve

KW - pregnancy

KW - reproductive age

KW - smoking habit

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common adult, middle age female

KW - anti-Muellerian hormone AMH 80497-65-0

KW - contraceptive drug contraceptive-drug oral administration

KW - follicle-stimulating hormone 9002-68-0

KW - 00520, General biology - Symposia, transactions and proceedings

KW - 10060, Biochemistry studies - General

KW - 12512, Pathology - Therapy

KW - 16504, Reproductive system - Physiology and biochemistry

KW - 22005, Pharmacology - Clinical pharmacology

KW - 22028, Pharmacology - Reproductive system and implantation studies

KW - Reproduction

KW - antral follicle reproductive system

KW - transvaginal sonography laboratory techniques, diagnostic techniques, clinical techniques, imaging and microscopy techniques

KW - Biochemistry and Molecular Biophysics

KW - Reproductive System

U2 - 10.1093/humrep/26.s1.3

DO - 10.1093/humrep/26.s1.3

M3 - Conference abstract in journal

VL - 26

SP - I4-I5

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - Suppl. 1

M1 - O-010

ER -