Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature
STUDY QUESTION Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause? SUMMARY ANSWER Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature...
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| Veröffentlicht in: | Human reproduction (Oxford) 2013-02, Vol.28 (2), p.488-495 |
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| creator | Thomas-Teinturier, Cécile El Fayech, Chiraz Oberlin, Odile Pacquement, Hélène Haddy, Nadia Labbé, Martine Veres, Cristina Guibout, Catherine Diallo, Ibrahima De Vathaire, Florent |
| description | STUDY QUESTION
Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause?
SUMMARY ANSWER
Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature menopause was uncommon. Main risk factors for non-surgical menopause were exposure to and dose of alkylating agents, especially during adolescence, radiation dose to the ovaries and oophorectomy.
WHAT IS KNOWN ALREADY
While survivors of childhood cancer are known to be at increased risk for developing premature menopause, data on its risk factors are limited.
STUDY DESIGN
A cohort study of 1109 still-living female survivors of childhood solid cancer treated between 1945 and 1985, of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
PARTICIPANTS AND METHODS
Seven hundred and six women, among whom 32% have attained 40 years of age, were included in this study. A Cox regression model was used to determine risk factors influencing the age at menopause.
MAIN RESULTS
Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7–28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8–108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries.
LIMITATIONS
The information on menopause was based on self-reported data without confirmation by FSH levels. Participants to this study have been treated for cancer from 1945 to 1985 and one can expect an increase in premature menopause incidence with more recent protocols using high-dose alkylating agents.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides data on risk factors for a reduced fertility window in order to inform survivors at risk and help oncologists to design new |
| doi_str_mv | 10.1093/humrep/des391 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1273584791</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/humrep/des391</oup_id><sourcerecordid>1273584791</sourcerecordid><originalsourceid>FETCH-LOGICAL-c392t-f9cb2ffb90174ac589f65731b71cace05c040360904e2468792e588cdbbbfbfd3</originalsourceid><addsrcrecordid>eNqFkDtPwzAURi0EoqUwsiKPLKF2nJfZqoqXVIkF5sh2rhujJA52XNR_T6oUGJnu6-i70kHompI7Sjhb1qF10C8r8IzTEzSnSUaimKXkFM1JnBURpRmdoQvvPwgZ2yI7R7OY0TQhWT5HX6stYDHgFjrbi-DHoauwGTw2nW4CdMp0W6yFGqw77LDAytbWDdhq7IPbmd3hMA6qNk1VW1thJToF7h6DcI0Bh2UYsBMOmj3uHbRiCA4u0ZkWjYerY12g98eHt_VztHl9elmvNpFiPB4izZWMtZac0DwRKi24ztKcUZlTJRSQVJGEsIxwkkCcZEXOY0iLQlVSSi11xRbodsrtnf0M4IeyNV5B04gObPAljXOWFknO6YhGE6qc9d6BLntnWuH2JSXlwXU5uS4n1yN_c4wOsoXql_6R-_fbhv6frG9xEIxt</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1273584791</pqid></control><display><type>article</type><title>Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature</title><source>MEDLINE</source><source>Oxford University Press Journals Current</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Thomas-Teinturier, Cécile ; El Fayech, Chiraz ; Oberlin, Odile ; Pacquement, Hélène ; Haddy, Nadia ; Labbé, Martine ; Veres, Cristina ; Guibout, Catherine ; Diallo, Ibrahima ; De Vathaire, Florent</creator><creatorcontrib>Thomas-Teinturier, Cécile ; El Fayech, Chiraz ; Oberlin, Odile ; Pacquement, Hélène ; Haddy, Nadia ; Labbé, Martine ; Veres, Cristina ; Guibout, Catherine ; Diallo, Ibrahima ; De Vathaire, Florent</creatorcontrib><description>STUDY QUESTION
Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause?
SUMMARY ANSWER
Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature menopause was uncommon. Main risk factors for non-surgical menopause were exposure to and dose of alkylating agents, especially during adolescence, radiation dose to the ovaries and oophorectomy.
WHAT IS KNOWN ALREADY
While survivors of childhood cancer are known to be at increased risk for developing premature menopause, data on its risk factors are limited.
STUDY DESIGN
A cohort study of 1109 still-living female survivors of childhood solid cancer treated between 1945 and 1985, of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
PARTICIPANTS AND METHODS
Seven hundred and six women, among whom 32% have attained 40 years of age, were included in this study. A Cox regression model was used to determine risk factors influencing the age at menopause.
MAIN RESULTS
Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7–28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8–108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries.
LIMITATIONS
The information on menopause was based on self-reported data without confirmation by FSH levels. Participants to this study have been treated for cancer from 1945 to 1985 and one can expect an increase in premature menopause incidence with more recent protocols using high-dose alkylating agents.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides data on risk factors for a reduced fertility window in order to inform survivors at risk and help oncologists to design new therapeutic protocols avoiding this risk. This study does not confirm the high rate of premature menopause reported by the Childhood Cancer Survivor Study, but this population differs from theirs (no leukemia and a lower percentage of lymphoma).
STUDY FUNDING
EDF, Ligue Nationale contre le cancer, IRESP, PHRC, AFSSAPS, Fondation Pfizer. No conflict of interest.</description><identifier>ISSN: 0268-1161</identifier><identifier>EISSN: 1460-2350</identifier><identifier>DOI: 10.1093/humrep/des391</identifier><identifier>PMID: 23154067</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Age Factors ; Antineoplastic Agents, Alkylating - administration & dosage ; Antineoplastic Agents, Alkylating - adverse effects ; Cohort Studies ; Female ; Humans ; Menopause ; Menopause, Premature ; Middle Aged ; Multivariate Analysis ; Neoplasms - complications ; Neoplasms - drug therapy ; Neoplasms - radiotherapy ; Ovary - radiation effects ; Ovary - surgery ; Radiotherapy - adverse effects ; Radiotherapy Dosage ; Regression Analysis ; Risk Factors ; Survivors</subject><ispartof>Human reproduction (Oxford), 2013-02, Vol.28 (2), p.488-495</ispartof><rights>The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-f9cb2ffb90174ac589f65731b71cace05c040360904e2468792e588cdbbbfbfd3</citedby><cites>FETCH-LOGICAL-c392t-f9cb2ffb90174ac589f65731b71cace05c040360904e2468792e588cdbbbfbfd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23154067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thomas-Teinturier, Cécile</creatorcontrib><creatorcontrib>El Fayech, Chiraz</creatorcontrib><creatorcontrib>Oberlin, Odile</creatorcontrib><creatorcontrib>Pacquement, Hélène</creatorcontrib><creatorcontrib>Haddy, Nadia</creatorcontrib><creatorcontrib>Labbé, Martine</creatorcontrib><creatorcontrib>Veres, Cristina</creatorcontrib><creatorcontrib>Guibout, Catherine</creatorcontrib><creatorcontrib>Diallo, Ibrahima</creatorcontrib><creatorcontrib>De Vathaire, Florent</creatorcontrib><title>Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature</title><title>Human reproduction (Oxford)</title><addtitle>Hum Reprod</addtitle><description>STUDY QUESTION
Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause?
SUMMARY ANSWER
Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature menopause was uncommon. Main risk factors for non-surgical menopause were exposure to and dose of alkylating agents, especially during adolescence, radiation dose to the ovaries and oophorectomy.
WHAT IS KNOWN ALREADY
While survivors of childhood cancer are known to be at increased risk for developing premature menopause, data on its risk factors are limited.
STUDY DESIGN
A cohort study of 1109 still-living female survivors of childhood solid cancer treated between 1945 and 1985, of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
PARTICIPANTS AND METHODS
Seven hundred and six women, among whom 32% have attained 40 years of age, were included in this study. A Cox regression model was used to determine risk factors influencing the age at menopause.
MAIN RESULTS
Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7–28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8–108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries.
LIMITATIONS
The information on menopause was based on self-reported data without confirmation by FSH levels. Participants to this study have been treated for cancer from 1945 to 1985 and one can expect an increase in premature menopause incidence with more recent protocols using high-dose alkylating agents.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides data on risk factors for a reduced fertility window in order to inform survivors at risk and help oncologists to design new therapeutic protocols avoiding this risk. This study does not confirm the high rate of premature menopause reported by the Childhood Cancer Survivor Study, but this population differs from theirs (no leukemia and a lower percentage of lymphoma).
STUDY FUNDING
EDF, Ligue Nationale contre le cancer, IRESP, PHRC, AFSSAPS, Fondation Pfizer. No conflict of interest.</description><subject>Adult</subject><subject>Age Factors</subject><subject>Antineoplastic Agents, Alkylating - administration & dosage</subject><subject>Antineoplastic Agents, Alkylating - adverse effects</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Menopause</subject><subject>Menopause, Premature</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neoplasms - complications</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - radiotherapy</subject><subject>Ovary - radiation effects</subject><subject>Ovary - surgery</subject><subject>Radiotherapy - adverse effects</subject><subject>Radiotherapy Dosage</subject><subject>Regression Analysis</subject><subject>Risk Factors</subject><subject>Survivors</subject><issn>0268-1161</issn><issn>1460-2350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAURi0EoqUwsiKPLKF2nJfZqoqXVIkF5sh2rhujJA52XNR_T6oUGJnu6-i70kHompI7Sjhb1qF10C8r8IzTEzSnSUaimKXkFM1JnBURpRmdoQvvPwgZ2yI7R7OY0TQhWT5HX6stYDHgFjrbi-DHoauwGTw2nW4CdMp0W6yFGqw77LDAytbWDdhq7IPbmd3hMA6qNk1VW1thJToF7h6DcI0Bh2UYsBMOmj3uHbRiCA4u0ZkWjYerY12g98eHt_VztHl9elmvNpFiPB4izZWMtZac0DwRKi24ztKcUZlTJRSQVJGEsIxwkkCcZEXOY0iLQlVSSi11xRbodsrtnf0M4IeyNV5B04gObPAljXOWFknO6YhGE6qc9d6BLntnWuH2JSXlwXU5uS4n1yN_c4wOsoXql_6R-_fbhv6frG9xEIxt</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Thomas-Teinturier, Cécile</creator><creator>El Fayech, Chiraz</creator><creator>Oberlin, Odile</creator><creator>Pacquement, Hélène</creator><creator>Haddy, Nadia</creator><creator>Labbé, Martine</creator><creator>Veres, Cristina</creator><creator>Guibout, Catherine</creator><creator>Diallo, Ibrahima</creator><creator>De Vathaire, Florent</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature</title><author>Thomas-Teinturier, Cécile ; El Fayech, Chiraz ; Oberlin, Odile ; Pacquement, Hélène ; Haddy, Nadia ; Labbé, Martine ; Veres, Cristina ; Guibout, Catherine ; Diallo, Ibrahima ; De Vathaire, Florent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-f9cb2ffb90174ac589f65731b71cace05c040360904e2468792e588cdbbbfbfd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Age Factors</topic><topic>Antineoplastic Agents, Alkylating - administration & dosage</topic><topic>Antineoplastic Agents, Alkylating - adverse effects</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Humans</topic><topic>Menopause</topic><topic>Menopause, Premature</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neoplasms - complications</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - radiotherapy</topic><topic>Ovary - radiation effects</topic><topic>Ovary - surgery</topic><topic>Radiotherapy - adverse effects</topic><topic>Radiotherapy Dosage</topic><topic>Regression Analysis</topic><topic>Risk Factors</topic><topic>Survivors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thomas-Teinturier, Cécile</creatorcontrib><creatorcontrib>El Fayech, Chiraz</creatorcontrib><creatorcontrib>Oberlin, Odile</creatorcontrib><creatorcontrib>Pacquement, Hélène</creatorcontrib><creatorcontrib>Haddy, Nadia</creatorcontrib><creatorcontrib>Labbé, Martine</creatorcontrib><creatorcontrib>Veres, Cristina</creatorcontrib><creatorcontrib>Guibout, Catherine</creatorcontrib><creatorcontrib>Diallo, Ibrahima</creatorcontrib><creatorcontrib>De Vathaire, Florent</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human reproduction (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thomas-Teinturier, Cécile</au><au>El Fayech, Chiraz</au><au>Oberlin, Odile</au><au>Pacquement, Hélène</au><au>Haddy, Nadia</au><au>Labbé, Martine</au><au>Veres, Cristina</au><au>Guibout, Catherine</au><au>Diallo, Ibrahima</au><au>De Vathaire, Florent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature</atitle><jtitle>Human reproduction (Oxford)</jtitle><addtitle>Hum Reprod</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>28</volume><issue>2</issue><spage>488</spage><epage>495</epage><pages>488-495</pages><issn>0268-1161</issn><eissn>1460-2350</eissn><abstract>STUDY QUESTION
Is the age at menopause in a cohort of childhood cancer survivors earlier and what are the risk factors associated with earlier age at menopause?
SUMMARY ANSWER
Menopause occurred at a median age of 44 years in this cohort which is earlier than in the general population, but premature menopause was uncommon. Main risk factors for non-surgical menopause were exposure to and dose of alkylating agents, especially during adolescence, radiation dose to the ovaries and oophorectomy.
WHAT IS KNOWN ALREADY
While survivors of childhood cancer are known to be at increased risk for developing premature menopause, data on its risk factors are limited.
STUDY DESIGN
A cohort study of 1109 still-living female survivors of childhood solid cancer treated between 1945 and 1985, of whom 863 (78%) returned a follow-up questionnaire. Of them, 157 were excluded.
PARTICIPANTS AND METHODS
Seven hundred and six women, among whom 32% have attained 40 years of age, were included in this study. A Cox regression model was used to determine risk factors influencing the age at menopause.
MAIN RESULTS
Ninety seven women have reached menopause at a median age of 44 years. Menopause has been surgically induced in 36% of women. In multivariate analysis, risk factors for non-surgical menopause included exposure to alkylating agents, increasing radiation dose to the ovaries, procarbazine dose, cyclophosphamide dose and unilateral oophorectomy. The highest risk ratio for non-surgical menopause was observed for women treated after the onset of puberty with alkylating agents, either alone (RR = 9, 95% CI: 2.7–28, P = 0.0003) or associated with even a low dose of radiation to the ovaries (RR = 29, 95% CI: 8–108, P < 0.0001). Exposure to unilateral oophorectomy is associated with a 7-year earlier age at menopause. By the age of 40, only 2.1% had non-surgical premature menopause and its main risk factors were age at diagnosis, cyclophosphamide dose, exposure to melphalan and radiation dose to the ovaries.
LIMITATIONS
The information on menopause was based on self-reported data without confirmation by FSH levels. Participants to this study have been treated for cancer from 1945 to 1985 and one can expect an increase in premature menopause incidence with more recent protocols using high-dose alkylating agents.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides data on risk factors for a reduced fertility window in order to inform survivors at risk and help oncologists to design new therapeutic protocols avoiding this risk. This study does not confirm the high rate of premature menopause reported by the Childhood Cancer Survivor Study, but this population differs from theirs (no leukemia and a lower percentage of lymphoma).
STUDY FUNDING
EDF, Ligue Nationale contre le cancer, IRESP, PHRC, AFSSAPS, Fondation Pfizer. No conflict of interest.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>23154067</pmid><doi>10.1093/humrep/des391</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0268-1161 |
| ispartof | Human reproduction (Oxford), 2013-02, Vol.28 (2), p.488-495 |
| issn | 0268-1161 1460-2350 |
| language | eng |
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| source | MEDLINE; Oxford University Press Journals Current; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Age Factors Antineoplastic Agents, Alkylating - administration & dosage Antineoplastic Agents, Alkylating - adverse effects Cohort Studies Female Humans Menopause Menopause, Premature Middle Aged Multivariate Analysis Neoplasms - complications Neoplasms - drug therapy Neoplasms - radiotherapy Ovary - radiation effects Ovary - surgery Radiotherapy - adverse effects Radiotherapy Dosage Regression Analysis Risk Factors Survivors |
| title | Age at menopause and its influencing factors in a cohort of survivors of childhood cancer: earlier but rarely premature |
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