Publication

Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced?

van Tilborg, T. C., Derks-Smeets, I. A. P., Bos, A. M. E., Oosterwijk, J. C., van Golde, R. J., de Die-Smulders, C. E., van der Kolk, L. E., van Zelst-Stams, W. A. G., Velthuizen, M. E., Hoek, A., Eijkemans, M. J. C., Laven, J. S. E., Ausems, M. G. E. M. & Broekmans, F. J. M., Nov-2016, In : Human Reproduction. 31, 11, p. 2651-2659 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

van Tilborg, T. C., Derks-Smeets, I. A. P., Bos, A. M. E., Oosterwijk, J. C., van Golde, R. J., de Die-Smulders, C. E., van der Kolk, L. E., van Zelst-Stams, W. A. G., Velthuizen, M. E., Hoek, A., Eijkemans, M. J. C., Laven, J. S. E., Ausems, M. G. E. M., & Broekmans, F. J. M. (2016). Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced? Human Reproduction, 31(11), 2651-2659. https://doi.org/10.1093/humrep/dew242

Author

van Tilborg, Theodora C. ; Derks-Smeets, Inge A. P. ; Bos, Anna M. E. ; Oosterwijk, Jan C. ; van Golde, Ron J. ; de Die-Smulders, Christine E. ; van der Kolk, Lizet E. ; van Zelst-Stams, Wendy A. G. ; Velthuizen, Maria E. ; Hoek, Annemieke ; Eijkemans, Marinus J. C. ; Laven, Joop S. E. ; Ausems, Margreet G. E. M. ; Broekmans, Frank J. M. / Serum AMH levels in healthy women from BRCA1/2 mutated families : are they reduced?. In: Human Reproduction. 2016 ; Vol. 31, No. 11. pp. 2651-2659.

Harvard

van Tilborg, TC, Derks-Smeets, IAP, Bos, AME, Oosterwijk, JC, van Golde, RJ, de Die-Smulders, CE, van der Kolk, LE, van Zelst-Stams, WAG, Velthuizen, ME, Hoek, A, Eijkemans, MJC, Laven, JSE, Ausems, MGEM & Broekmans, FJM 2016, 'Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced?', Human Reproduction, vol. 31, no. 11, pp. 2651-2659. https://doi.org/10.1093/humrep/dew242

Standard

Serum AMH levels in healthy women from BRCA1/2 mutated families : are they reduced? / van Tilborg, Theodora C.; Derks-Smeets, Inge A. P.; Bos, Anna M. E.; Oosterwijk, Jan C.; van Golde, Ron J.; de Die-Smulders, Christine E.; van der Kolk, Lizet E.; van Zelst-Stams, Wendy A. G.; Velthuizen, Maria E.; Hoek, Annemieke; Eijkemans, Marinus J. C.; Laven, Joop S. E.; Ausems, Margreet G. E. M.; Broekmans, Frank J. M.

In: Human Reproduction, Vol. 31, No. 11, 11.2016, p. 2651-2659.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van Tilborg TC, Derks-Smeets IAP, Bos AME, Oosterwijk JC, van Golde RJ, de Die-Smulders CE et al. Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced? Human Reproduction. 2016 Nov;31(11):2651-2659. https://doi.org/10.1093/humrep/dew242


BibTeX

@article{79a6f9f8563d454f9018cfb2af416883,
title = "Serum AMH levels in healthy women from BRCA1/2 mutated families: are they reduced?",
abstract = "Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Mullerian hormone (AMH) levels?BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders.It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan.A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 A mu g/l (SD +/- 0.12 A mu g/l, two-sided alpha-error 0.05, power 80%).Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels.Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 A mu g/l [0.11-19.00] compared to 1.80 A mu g/l [0.11-10.00] in non-carriers (P = 0.34). Adjusted linear regression analysis revealed no reduction in AMH level in the carriers (relative change = 0.98 (95%CI, 0.77-1.22); P = 0.76).Participants were relatively young. Power was insufficient to analyze BRCA1 and BRCA2 mutation carriers separately. AMH levels may have been influenced by the use of hormonal contraceptives, though similar proportions of carriers and non-carriers were current users and adjustments were made to correct for potential confounding in our analysis.Limitations of the current analysis and limitations of the existing literature argue for prospective, well-controlled follow-up studies with recurrent AMH measurements to determine whether carriers might be at risk for low ovarian reserve and to definitively guide care.This study was partially financially supported by a personal grant for Inge A.P. Derks-Smeets, kindly provided by the Dutch Cancer Society (Grant Number UM 2011-5249). Theodora C. van Tilborg, Inge A.P. Derks-Smeets, Anna M.E. Bos, Jan C. Oosterwijk, Christine E. de Die-Smulders, Lizet E. van der Kolk, Wendy A.G. van Zelst-Stams, Maria E. Velthuizen, Marinus J.C. Eijkemans and Margreet G.E.M. Ausems have nothing to disclose. Ron J. van Golde has received unrestricted research grants from Ferring and Merck Serono, outside the submitted work. Annemieke Hoek received an unrestricted educational grant from Ferring pharmaceutical BV, The Netherlands and a speaker's fee for post graduate education from MSD pharmaceutical company, outside the submitted work. Joop S.E. Laven has received unrestricted research grants from Ferring, Merck Serono, Merck Sharpe & Dome, Organon, and Schering Plough, outside the submitted work. Frank J.M. Broekmans is a member of the external advisory board for Merck Serono (The Netherlands), outside the submitted work.NTR no. 4324.",
keywords = "anti-Mullerian hormone, BRCA mutation, ovarian reserve, ovarian aging, genes, ANTI-MLLERIAN HORMONE, NATURAL MENOPAUSE, OVARIAN RESERVE, ANTIMULLERIAN HORMONE, PREMATURE MENOPAUSE, DNA-REPAIR, BREAST/OVARIAN CANCER, FEMALE FERTILITY, BREAST-CANCER, AGE",
author = "{van Tilborg}, {Theodora C.} and Derks-Smeets, {Inge A. P.} and Bos, {Anna M. E.} and Oosterwijk, {Jan C.} and {van Golde}, {Ron J.} and {de Die-Smulders}, {Christine E.} and {van der Kolk}, {Lizet E.} and {van Zelst-Stams}, {Wendy A. G.} and Velthuizen, {Maria E.} and Annemieke Hoek and Eijkemans, {Marinus J. C.} and Laven, {Joop S. E.} and Ausems, {Margreet G. E. M.} and Broekmans, {Frank J. M.}",
note = "{\textcopyright} The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2016",
month = nov,
doi = "10.1093/humrep/dew242",
language = "English",
volume = "31",
pages = "2651--2659",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Serum AMH levels in healthy women from BRCA1/2 mutated families

T2 - are they reduced?

AU - van Tilborg, Theodora C.

AU - Derks-Smeets, Inge A. P.

AU - Bos, Anna M. E.

AU - Oosterwijk, Jan C.

AU - van Golde, Ron J.

AU - de Die-Smulders, Christine E.

AU - van der Kolk, Lizet E.

AU - van Zelst-Stams, Wendy A. G.

AU - Velthuizen, Maria E.

AU - Hoek, Annemieke

AU - Eijkemans, Marinus J. C.

AU - Laven, Joop S. E.

AU - Ausems, Margreet G. E. M.

AU - Broekmans, Frank J. M.

N1 - © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2016/11

Y1 - 2016/11

N2 - Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Mullerian hormone (AMH) levels?BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders.It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan.A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 A mu g/l (SD +/- 0.12 A mu g/l, two-sided alpha-error 0.05, power 80%).Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels.Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 A mu g/l [0.11-19.00] compared to 1.80 A mu g/l [0.11-10.00] in non-carriers (P = 0.34). Adjusted linear regression analysis revealed no reduction in AMH level in the carriers (relative change = 0.98 (95%CI, 0.77-1.22); P = 0.76).Participants were relatively young. Power was insufficient to analyze BRCA1 and BRCA2 mutation carriers separately. AMH levels may have been influenced by the use of hormonal contraceptives, though similar proportions of carriers and non-carriers were current users and adjustments were made to correct for potential confounding in our analysis.Limitations of the current analysis and limitations of the existing literature argue for prospective, well-controlled follow-up studies with recurrent AMH measurements to determine whether carriers might be at risk for low ovarian reserve and to definitively guide care.This study was partially financially supported by a personal grant for Inge A.P. Derks-Smeets, kindly provided by the Dutch Cancer Society (Grant Number UM 2011-5249). Theodora C. van Tilborg, Inge A.P. Derks-Smeets, Anna M.E. Bos, Jan C. Oosterwijk, Christine E. de Die-Smulders, Lizet E. van der Kolk, Wendy A.G. van Zelst-Stams, Maria E. Velthuizen, Marinus J.C. Eijkemans and Margreet G.E.M. Ausems have nothing to disclose. Ron J. van Golde has received unrestricted research grants from Ferring and Merck Serono, outside the submitted work. Annemieke Hoek received an unrestricted educational grant from Ferring pharmaceutical BV, The Netherlands and a speaker's fee for post graduate education from MSD pharmaceutical company, outside the submitted work. Joop S.E. Laven has received unrestricted research grants from Ferring, Merck Serono, Merck Sharpe & Dome, Organon, and Schering Plough, outside the submitted work. Frank J.M. Broekmans is a member of the external advisory board for Merck Serono (The Netherlands), outside the submitted work.NTR no. 4324.

AB - Do BRCA1/2 mutation carriers have a compromised ovarian reserve compared to proven non-carriers, based on serum anti-Mullerian hormone (AMH) levels?BRCA1/2 mutation carriers do not show a lower serum AMH level in comparison to proven non-carriers, after adjustment for potential confounders.It has been suggested that the BRCA genes play a role in the process of ovarian reserve depletion, although previous studies have shown inconsistent results regarding the association between serum AMH levels and BRCA mutation status. Hence, it is yet unclear whether BRCA1/2 mutation carriers may indeed be at risk of a reduced reproductive lifespan.A multicenter, cross-sectional study was performed between January 2012 and February 2015 in 255 women. We needed to include 120 BRCA1/2 mutation carriers and 120 proven non-carriers to demonstrate a difference in AMH levels of 0.40 A mu g/l (SD +/- 0.12 A mu g/l, two-sided alpha-error 0.05, power 80%).Healthy women aged 18-45 years who were referred to the Clinical Genetics Department and applied for predictive BRCA1/2 testing because of a familial BRCA1/2 mutation were asked to participate. A cross-sectional assessment was performed by measuring serum AMH levels and filling out a questionnaire. Multivariate linear regression analyses adjusted for age, current smoking and current hormonal contraceptive use were performed on log-transformed serum AMH levels.Out of 823 potentially eligible women, 421 (51.2%) were willing to participate, and of those, 166 (39%) did not meet our inclusion criteria. Two hundred and fifty-five women were available for analyses; 124 BRCA1/2 mutation carriers and 131 proven non-carriers. The median [range] AMH level in carriers was 1.90 A mu g/l [0.11-19.00] compared to 1.80 A mu g/l [0.11-10.00] in non-carriers (P = 0.34). Adjusted linear regression analysis revealed no reduction in AMH level in the carriers (relative change = 0.98 (95%CI, 0.77-1.22); P = 0.76).Participants were relatively young. Power was insufficient to analyze BRCA1 and BRCA2 mutation carriers separately. AMH levels may have been influenced by the use of hormonal contraceptives, though similar proportions of carriers and non-carriers were current users and adjustments were made to correct for potential confounding in our analysis.Limitations of the current analysis and limitations of the existing literature argue for prospective, well-controlled follow-up studies with recurrent AMH measurements to determine whether carriers might be at risk for low ovarian reserve and to definitively guide care.This study was partially financially supported by a personal grant for Inge A.P. Derks-Smeets, kindly provided by the Dutch Cancer Society (Grant Number UM 2011-5249). Theodora C. van Tilborg, Inge A.P. Derks-Smeets, Anna M.E. Bos, Jan C. Oosterwijk, Christine E. de Die-Smulders, Lizet E. van der Kolk, Wendy A.G. van Zelst-Stams, Maria E. Velthuizen, Marinus J.C. Eijkemans and Margreet G.E.M. Ausems have nothing to disclose. Ron J. van Golde has received unrestricted research grants from Ferring and Merck Serono, outside the submitted work. Annemieke Hoek received an unrestricted educational grant from Ferring pharmaceutical BV, The Netherlands and a speaker's fee for post graduate education from MSD pharmaceutical company, outside the submitted work. Joop S.E. Laven has received unrestricted research grants from Ferring, Merck Serono, Merck Sharpe & Dome, Organon, and Schering Plough, outside the submitted work. Frank J.M. Broekmans is a member of the external advisory board for Merck Serono (The Netherlands), outside the submitted work.NTR no. 4324.

KW - anti-Mullerian hormone

KW - BRCA mutation

KW - ovarian reserve

KW - ovarian aging

KW - genes

KW - ANTI-MLLERIAN HORMONE

KW - NATURAL MENOPAUSE

KW - OVARIAN RESERVE

KW - ANTIMULLERIAN HORMONE

KW - PREMATURE MENOPAUSE

KW - DNA-REPAIR

KW - BREAST/OVARIAN CANCER

KW - FEMALE FERTILITY

KW - BREAST-CANCER

KW - AGE

U2 - 10.1093/humrep/dew242

DO - 10.1093/humrep/dew242

M3 - Article

C2 - 27907901

VL - 31

SP - 2651

EP - 2659

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 11

ER -

ID: 38600469