<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="letter" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">Gates Open Res</journal-id>
            <journal-title-group>
                <journal-title>Gates Open Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2572-4754</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/gatesopenres.13609.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Open Letter</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Global research and learning agenda for building evidence on contraceptive-induced menstrual changes for research, product development, policies, and programs</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 2 approved]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Hoppes</surname>
                        <given-names>Emily</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-0178-4068</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Nwachukwu</surname>
                        <given-names>Chukwuemeka</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Hennegan</surname>
                        <given-names>Julie</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Blithe</surname>
                        <given-names>Diana L.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Cordova-Gomez</surname>
                        <given-names>Amanda</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Critchley</surname>
                        <given-names>Hilary</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-1913-4044</uri>
                    <xref ref-type="aff" rid="a5">5</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Doncel</surname>
                        <given-names>Gustavo F.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a6">6</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Dorflinger</surname>
                        <given-names>Laneta J.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Haddad</surname>
                        <given-names>Lisa B.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a7">7</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mackenzie</surname>
                        <given-names>Amelia C.L.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-1721-805X</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Maybin</surname>
                        <given-names>Jacqueline A.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a5">5</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Moley</surname>
                        <given-names>Kelle</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a8">8</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Nanda</surname>
                        <given-names>Kavita</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-7650-2929</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sales Vieira</surname>
                        <given-names>Carolina</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a9">9</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Vwalika</surname>
                        <given-names>Bellington</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a10">10</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Kibira</surname>
                        <given-names>Simon P.S.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-7385-423X</uri>
                    <xref ref-type="aff" rid="a11">11</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mickler</surname>
                        <given-names>Alexandria</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>OlaOlorun</surname>
                        <given-names>Funmilola M.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-5544-2875</uri>
                    <xref ref-type="aff" rid="a12">12</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Polis</surname>
                        <given-names>Chelsea B.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-1031-7074</uri>
                    <xref ref-type="aff" rid="a13">13</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sommer</surname>
                        <given-names>Marni</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a14">14</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Williams</surname>
                        <given-names>Katie M.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-7643-5383</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Lathrop</surname>
                        <given-names>Eva</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a15">15</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Mahajan</surname>
                        <given-names>Tanya</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a16">16</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Rademacher</surname>
                        <given-names>Kate H.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-7015-5073</uri>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Solomon</surname>
                        <given-names>Marsden</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Wilson</surname>
                        <given-names>Katrina</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a17">17</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Wilson</surname>
                        <given-names>Lucy C.</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a18">18</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Rountree</surname>
                        <given-names>Lillian</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>FHI 360, Durham, NC, 27701, USA</aff>
                <aff id="a2">
                    <label>2</label>United States Agency for International Development (USAID), Washington, District of Columbia, 20523, USA</aff>
                <aff id="a3">
                    <label>3</label>Maternal Child and Adolescent Health Program, Burnet Institute, Melbourne, VIC 3004, Australia</aff>
                <aff id="a4">
                    <label>4</label>Contraceptive Development Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892, USA</aff>
                <aff id="a5">
                    <label>5</label>MRC Centre for Reproductive Health, Queen&#x2019;s Medical Research Institute, University of Edinburgh, Edinburgh, EH8 9YL, UK</aff>
                <aff id="a6">
                    <label>6</label>CONRAD, Eastern Virginia Medical School, Norfolk, Virginia, 23507, USA</aff>
                <aff id="a7">
                    <label>7</label>Center for Biomedical Research, Population Council, New York, New York, 10017, USA</aff>
                <aff id="a8">
                    <label>8</label>Bill &amp; Melinda Gates Foundation, Seattle, Washington, 98109, USA</aff>
                <aff id="a9">
                    <label>9</label>Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of S&#x00e3;o Paulo, S&#x00e3;o Paulo, Brazil</aff>
                <aff id="a10">
                    <label>10</label>Departments of Obstetrics and Gynaecology, University of Zambia School of Medicine, Lusaka, Zambia</aff>
                <aff id="a11">
                    <label>11</label>Department of Community Health and Behavioural Sciences, School of Public Health, Makerere University, Kampala, Uganda</aff>
                <aff id="a12">
                    <label>12</label>Department of Community Medicine, University of Ibadan, Ibadan, Nigeria</aff>
                <aff id="a13">
                    <label>13</label>Independent Researcher, Brooklyn, New York, USA</aff>
                <aff id="a14">
                    <label>14</label>Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York, New York, 10032, USA</aff>
                <aff id="a15">
                    <label>15</label>Population Services International, Washington, District of Columbia, 20526, USA</aff>
                <aff id="a16">
                    <label>16</label>The Pad Project, New Delhi, India</aff>
                <aff id="a17">
                    <label>17</label>MSI Reproductive Choices, London, W1T 6LP, UK</aff>
                <aff id="a18">
                    <label>18</label>Rising Outcomes, Hillsborough, NC, 27278, USA</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:ehoppes@fhi360.org">ehoppes@fhi360.org</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>19</day>
                <month>4</month>
                <year>2022</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2022</year>
            </pub-date>
            <volume>6</volume>
            <elocation-id>49</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>12</day>
                    <month>4</month>
                    <year>2022</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Hoppes E et al.</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://gatesopenresearch.org/articles/6-49/pdf"/>
            <abstract>
                <p>
                    <bold>Background</bold>: Contraceptive-induced menstrual changes (CIMCs) can affect family planning (FP) users&#x2019; lives in both positive and negative ways, resulting in both opportunities and consequences. Despite this, and despite the important links between FP and menstrual health (MH), neither field adequately addresses CIMCs, including in research, product development, policies, and programs globally.</p>
                <p>
                    <bold>Methods</bold>: In November 2020, a convening of both MH and FP experts reviewed the existing evidence on CIMCs and identified significant gaps in key areas.</p>
                <p>
                    <bold>Results</bold>: These gaps led to the establishment of a CIMC Task Force in April 2021 and the development of the 
                    <italic toggle="yes">Global Research and Learning Agenda: Building Evidence on Contraceptive-Induced Menstrual Changes in Research, Product Development, Policies, and Programs Globally</italic> (the CIMC RLA), which includes four research agendas for (1) measurement, (2) contraceptive research and development (R&amp;D) and biomedical research, (3) social-behavioral and user preferences research, and (4) programmatic research.</p>
                <p>
                    <bold>Conclusions</bold>: Guided by the CIMC RLA, researchers, product developers, health care providers, program implementers, advocates, policymakers, and funders are urged to conduct research and implement strategies to address the beneficial and negative effects of CIMCs and support the integration of FP and MH. CIMCs need to be addressed to improve the health and well-being of women, girls, and other people who menstruate and use contraceptives globally.</p>
                <p>
                    <bold>
                        <italic toggle="yes">Disclaimer</italic>
                    </bold>: 
                    <italic toggle="yes">The views expressed in this article are those of the authors. Publication in Gates Open Research does not imply endorsement by the Gates Foundation.</italic>
                </p>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>family planning</kwd>
                <kwd>contraceptive</kwd>
                <kwd>menstrual health</kwd>
                <kwd>contraceptive-induced menstrual change</kwd>
                <kwd>CIMC</kwd>
                <kwd>menstrual change</kwd>
                <kwd>research agenda</kwd>
                <kwd>research and learning agenda</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>USAID</funding-source>
                    <award-id>7200AA20CA00016</award-id>
                    <award-id>7200AA19CA00041</award-id>
                </award-group>
                <award-group id="fund-2">
                    <funding-source>Reckitt Global Hygiene Institute (RGHI)</funding-source>
                </award-group>
                <award-group id="fund-3">
                    <funding-source>The Sid and Helaine Lerner MHM Faculty Support Fund</funding-source>
                </award-group>
                <award-group id="fund-4">
                    <funding-source>Wellcome Trust Fellowship</funding-source>
                    <award-id>209589/Z/17/</award-id>
                </award-group>
                <funding-statement>This work was supported by the Gates Foundation [OPP1200867].&#13;
&#13;
The development of this manuscript was also funded by the Innovate FP and Research for Scalable Solutions projects and is made possible by the support of the American People through the United States Agency for International Development (USAID). The contents of this brief are the sole responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government.&#13;
&#13;
J. Hennegan's time on this work was funded in part by the Reckitt Global Hygiene Institute (RGHI). The views expressed are those of the authors and not necessarily those of RGHI.&#13;
&#13;
M. Sommer's time on this work was funded in part by The Sid and Helaine Lerner MHM Faculty Support Fund. The views expressed are those of the authors and not necessarily those of The Sid and Helaine Lerner MHM Faculty Support Fund.&#13;
&#13;
J.A. Maybin&#x2019;s time was funded by the Wellcome Trust Fellowship [209589/Z/17/].</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec sec-type="intro">
            <title>Introduction</title>
            <p>Contraceptive-induced menstrual changes (CIMCs) affect contraceptive users&#x2019; lives in both positive and negative ways. These include consequences such as dissatisfaction with and discontinuation of contraceptives, as well as opportunities
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>
                </sup>, such as improved quality of life and potential treatment of menstrual disorders
                <sup>
                    <xref ref-type="bibr" rid="ref-2">2</xref>
                </sup>. Despite the important links between family planning (FP) and menstrual health (MH),
                <sup>
                    <xref ref-type="other" rid="FN1">a</xref>
                </sup> neither field adequately addresses CIMCs, including in research, product development, policies, and programs globally.</p>
        </sec>
        <sec>
            <title>Contraceptive-induced menstrual changes</title>
            <p>CIMCs encompass all changes to a users&#x2019; menstrual cycle caused by using contraception, including:</p>
            <list list-type="bullet">
                <list-item>
                    <p>Changes in bleeding duration, volume, frequency, and/or regularity/predictability</p>
                </list-item>
                <list-item>
                    <p>Changes in blood (and other uterine and cervical effluent) consistency, color, and/or smell</p>
                </list-item>
                <list-item>
                    <p>Changes in uterine cramping and pain</p>
                </list-item>
                <list-item>
                    <p>Changes in other symptoms before, during, and after menstruation (e.g., migraines, breast tenderness, gastrointestinal symptoms) </p>
                </list-item>
                <list-item>
                    <p>Changes in experiences of menstrual and gynecologic disorders and symptoms
                        <sup>
                            <xref ref-type="other" rid="FN2">b</xref>
                        </sup>
                    </p>
                </list-item>
                <list-item>
                    <p>Changes over time with continued contraceptive method use</p>
                </list-item>
                <list-item>
                    <p>Short-term changes to the menstrual cycle after contraceptive discontinuation</p>
                </list-item>
            </list>
            <p>Some individuals dislike CIMCs, which can contribute to dissatisfaction or discontinuation or non-use of contraception
                <sup>
                    <xref ref-type="bibr" rid="ref-1">1</xref>,
                    <xref ref-type="bibr" rid="ref-3">3</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref-5">5</xref>
                </sup>. These negative reactions are the result of the varied and real impacts of CIMCs on users&#x2019; lives and their beliefs surrounding menstruation. CIMCs, particularly heavier, longer, irregular, or painful bleeding, may exacerbate difficulties in managing menstruation, including changes in the quantity or type of menstrual materials needed, increased need for analgesics, and an increase in the need for safe, private, accessible water, sanitation, and hygiene (WASH) facilities
                <sup>
                    <xref ref-type="bibr" rid="ref-6">6</xref>,
                    <xref ref-type="bibr" rid="ref-7">7</xref>
                </sup>. In addition, CIMCs can have significant effects on users&#x2019; abilities to participate in regular activities like school, work, sex, and social and religious activities
                <sup>
                    <xref ref-type="bibr" rid="ref-4">4</xref>,
                    <xref ref-type="bibr" rid="ref-8">8</xref>
                </sup>. For example, in some contexts, social norms inhibit users from participating in religious practices or household work like cooking when they are menstruating
                <sup>
                    <xref ref-type="bibr" rid="ref-10">10</xref>
                </sup>. CIMCs can also be associated with psychosocial impacts caused by the stress of managing these changes and worry related to hiding CIMCs among those trying to use their contraceptive method discreetly
                <sup>
                    <xref ref-type="bibr" rid="ref-11">11</xref>
                </sup>. CIMCs can also negatively affect sexual satisfaction and well-being
                <sup>
                    <xref ref-type="bibr" rid="ref-12">12</xref>
                </sup>. In addition, beliefs about CIMCs can reduce individuals&#x2019; motivation to begin or continue using contraception, and can influence the attitudes and behaviors of providers
                <sup>
                    <xref ref-type="bibr" rid="ref-13">13</xref>
                </sup>. Some contraceptive users fear that CIMCs indicate, or can lead to, negative health consequences, especially bleeding that is heavier in volume or longer in duration. On the other hand, some users may fear that contraceptive-induced amenorrhea&#x2014;or paused bleeding&#x2014;means there is a buildup of &#x201c;dirty&#x201d; or &#x201c;bad&#x201d; blood in their bodies that might indicate or lead to major health issues including infertility, although these are not clinically documented health effects of contraceptive-induced amenorrhea
                <sup>
                    <xref ref-type="bibr" rid="ref-4">4</xref>,
                    <xref ref-type="bibr" rid="ref-14">14</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref-16">16</xref>
                </sup>.</p>
            <p>CIMCs can also have advantages that motivate individuals to begin and/or continue contraceptive use. Reduced menstrual bleeding, pain, or cramping, as well as paused bleeding can offer increased freedom to engage in regular activities, improved convenience, improved sexual satisfaction, decreased stress and worry, and reduced spending if fewer menstrual materials are needed
                <sup>
                    <xref ref-type="bibr" rid="ref-2">2</xref>,
                    <xref ref-type="bibr" rid="ref-17">17</xref>
                </sup>. Some individuals choose to use contraception primarily, or at least in part, for the resulting beneficial menstrual changes, including the management of menstrual and gynecologic disorders and symptoms, such as heavy menstrual bleeding, which affects approximately 30 percent of those who menstruate
                <sup>
                    <xref ref-type="bibr" rid="ref-18">18</xref>
                </sup>, and endometriosis, which affects an estimated 10% of menstruators worldwide
                <sup>
                    <xref ref-type="bibr" rid="ref-19">19</xref>
                </sup>. Contraceptives that reduce bleeding may also prevent or improve other health conditions, including iron deficiency and iron deficiency anemia, which can be caused by heavy menstrual bleeding and affects about a third of women of reproductive age globally
                <sup>
                    <xref ref-type="bibr" rid="ref-20">20</xref>
                </sup>. Finally, CIMCs can be beneficial for transgender and gender expansive persons who may use contraceptives to induce amenorrhea and reduce the effects menstruation may have on gender dysphoria
                <sup>
                    <xref ref-type="bibr" rid="ref-21">21</xref>
                </sup>.</p>
            <sec>
                <title>Evidence and knowledge gaps</title>
                <p>In November 2020, a convening of both MH and FP experts reviewed the existing evidence on CIMCs and identified significant gaps in key areas
                    <sup>
                        <xref ref-type="bibr" rid="ref-22">22</xref>
                    </sup>. Critically, not enough is known about the biological mechanisms that underlie CIMCs; therefore, therapies for preventing undesired CIMCs and for prolonging desired CIMCs lack a robust mechanistic foundation
                    <sup>
                        <xref ref-type="bibr" rid="ref-23">23</xref>
                    </sup>. This lack of mechanistic knowledge impacts the potential for research and development (R&amp;D) to lead to new and innovative contraceptives that might also be treatments for menstrual and gynecologic disorders and symptoms
                    <sup>
                        <xref ref-type="bibr" rid="ref-24">24</xref>
                    </sup>. While evidence exists around the preferences of contraceptive users related to CIMCs, not enough is known about the social and relational influences that shape these preferences and existing evidence is from a limited population that lacks diversity. More research is needed to understand the full impact of CIMCs on contraceptive use, menstrual health, and quality of life
                    <sup>
                        <xref ref-type="bibr" rid="ref-4">4</xref>,
                        <xref ref-type="bibr" rid="ref-25">25</xref>
                    </sup>. There is also a substantial evidence gap in understanding the most effective programs and interventions to address CIMCs, including ideal approaches for counseling and the potential impact of integrating FP services and MH services
                    <sup>
                        <xref ref-type="other" rid="FN3">c</xref>
                    </sup>
                    <sup>
                        <xref ref-type="bibr" rid="ref-26">26</xref>,
                        <xref ref-type="bibr" rid="ref-27">27 </xref>
                    </sup>. Finally, a lack of standardized and validated measures for different aspects of CIMCs and harmonization across the measurement of biological mechanisms, user preferences, social influences, impacts, and programs compounds the evidence gap
                    <sup>
                        <xref ref-type="bibr" rid="ref-22">22</xref>
                    </sup>.</p>
                <p>These gaps led to the establishment of a CIMC Task Force in April 2021 and the development of the 
                    <bold>
                        <italic toggle="yes">Global Research and Learning Agenda: Building Evidence on Contraceptive-Induced Menstrual Changes in Research, Product Development, Policies, and Programs Globally,</italic>
                    </bold> referred to below as the &#x201c;CIMC RLA&#x201d;
                    <sup>
                        <xref ref-type="bibr" rid="ref-28">28</xref>
                    </sup>.</p>
            </sec>
        </sec>
        <sec>
            <title>The contraceptive-induced menstrual changes global research and learning agenda</title>
            <p>The CIMC RLA includes four research agendas focused on: (1) measurement, (2) contraceptive research and development (R&amp;D) and biomedical research, (3) social-behavioral and user preferences research, and (4) programmatic research. It was developed to provide guidance to researchers, product developers, health care providers, program implementers, advocates, policymakers, and funders interested in expanding understanding of CIMCs. For all four agendas, it is essential that research is conducted with diverse populations across different locations, races and ethnicities, socio-economic status, ages, abilities/disabilities, sexual orientations, and gender identities, and that researchers recognize the complexity and intersection of identities that play a role in people&#x2019;s perceptions, experiences, and behavior. In addition, groups who have been historically systematically marginalized or underserved should be involved to the extent possible in this research, including youth, perimenopausal people, people with disabilities, people living with HIV, postpartum people, refugees, migrants or other mobile populations, sex workers, people in the LGBTQ (lesbian, gay, bisexual, transgender, queer) community, survivors of abuse and violence, and those who are incarcerated.</p>
            <sec>
                <title>Measurement research agenda</title>
                <p>Across research efforts, the measurements used shape what is learned. For CIMCs, an integrated and interdisciplinary approach is needed to ensure essential concepts are identified and measured appropriately. 
                    <xref ref-type="fig" rid="f1">Figure 1</xref> provides the full measurement research agenda. Future CIMC research and programs should be informed by a harmonized measurement framework that includes indicators related to biological changes, social environments, facilities and services, user experiences, preferences, and behaviors, and impacts on health and life (
                    <xref ref-type="fig" rid="f2">Figure 2</xref>). As a priority, those working in CIMC research should review the indicators and tools being used across disciplines to identify opportunities for standardization and gaps to be addressed. </p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>Figure 1. </label>
                    <caption>
                        <title>Measurement Research Agenda for Contraceptive-Induced Menstrual Changes.</title>
                    </caption>
                    <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/14882/2d099065-4f1e-4558-8533-0d830459590f_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>Figure 2. </label>
                    <caption>
                        <title>Contraceptive-Induced Menstrual Changes Measurement Framework.</title>
                    </caption>
                    <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/14882/2d099065-4f1e-4558-8533-0d830459590f_figure2.gif"/>
                </fig>
            </sec>
            <sec>
                <title>Contraceptive R&amp;D and biomedical research agenda</title>
                <p>The full agenda for contraceptive R&amp;D and biomedical research is provided in 
                    <xref ref-type="fig" rid="f3">Figure 3</xref>. Research in this area should focus on: (1) understanding the biological mechanisms that lead to CIMCs and factors that affect these mechanisms; (2) developing evidence-based prevention and treatment options for undesired CIMCs and options to accelerate and maintain desired CIMCs; and (3) understanding the use of existing and new contraceptive methods to treat menstrual and gynecologic disorders and symptoms. This work should integrate users&#x2019; preferences and needs related to CIMCs into product development. As a priority, researchers should work to streamline and improve research definitions, measurement, methodologies, and analyses.</p>
                <fig fig-type="figure" id="f3" orientation="portrait" position="float">
                    <label>Figure 3. </label>
                    <caption>
                        <title>Contraceptive R&amp;D and Biomedical Research Agenda for Contraceptive-Induced Menstrual Changes.</title>
                    </caption>
                    <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/14882/2d099065-4f1e-4558-8533-0d830459590f_figure3.gif"/>
                </fig>
            </sec>
            <sec>
                <title>Social behavioral and user preferences research agenda</title>
                <p>
                    <xref ref-type="fig" rid="f4">Figure 4</xref> provides the agenda for better understanding users&#x2019; perceptions, attitudes, and experiences related to CIMCs. Future social-behavioral research should seek to understand: (1) the nuance and diversity of perceptions, attitudes, and practices related to all types of CIMCs; (2) the factors that influence CIMC perceptions, attitudes, and practices, including at the individual, interpersonal, and wider socio-ecological levels and across the life course; and (3) the impacts of CIMCs on users&#x2019; lives, including their FP and MH practices and decision-making. As a priority, socio-behavioral researchers should assess the state and strength of the existing evidence related to CIMC perceptions.</p>
                <fig fig-type="figure" id="f4" orientation="portrait" position="float">
                    <label>Figure 4. </label>
                    <caption>
                        <title>Social Behavioral and User Preferences Research Agenda for Contraceptive-Induced Menstrual Changes.</title>
                    </caption>
                    <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/14882/2d099065-4f1e-4558-8533-0d830459590f_figure4.gif"/>
                </fig>
            </sec>
            <sec>
                <title>Programmatic research agenda</title>
                <p>When designing and testing ways to address CIMCs through education, counseling, and provision of services, it is important to monitor progress, evaluate impact on a wide variety of measures related to CIMCs, MH, FP, and other areas of sexual and reproductive health and rights (SRHR), and assess the cost-effectiveness of various approaches as well as equity in access. It is also critical to document successes and failures, adjust services accordingly, and disseminate findings to key stakeholders. Key evaluation questions that can be included in implementation science and routine or enhanced monitoring and evaluation are outlined in 
                    <xref ref-type="fig" rid="f5">Figure 5</xref>. Future programmatic research should prioritize identifying, defining, and designing how FP and MH can be effectively integrated, including to address CIMCs.</p>
                <fig fig-type="figure" id="f5" orientation="portrait" position="float">
                    <label>Figure 5. </label>
                    <caption>
                        <title>Programmatic Research Agenda for Contraceptive-Induced Menstrual Changes.</title>
                    </caption>
                    <graphic orientation="portrait" position="float" xlink:href="https://gatesopenresearch-files.f1000.com/manuscripts/14882/2d099065-4f1e-4558-8533-0d830459590f_figure5.gif"/>
                </fig>
            </sec>
            <sec>
                <title>Cross-cutting considerations and foundations</title>
                <p>The CIMC RLA is grounded in the socioecological model
                    <sup>
                        <xref ref-type="bibr" rid="ref-29">29</xref>
                    </sup> and a life course approach
                    <sup>
                        <xref ref-type="bibr" rid="ref-30">30</xref>
                    </sup>. Therefore, we call for research related to CIMCs to: (1) consider the impact of different levels of socio-ecological influence; (2) consider the changing experiences and preferences of users across the reproductive life course, from menarche to menopause; (3) integrate equity using a rights-based framework including considerations for social and environmental determinants of health; and (4) consider and incorporate equity, choice, gender, and self-care.</p>
            </sec>
        </sec>
        <sec sec-type="conclusions">
            <title>Conclusion</title>
            <p>Guided by the CIMC RLA, researchers, product developers, health care providers, program implementers, advocates, policymakers, and funders are urged to conduct research and implement strategies to address the beneficial and negative effects of CIMCs and support the integration of FP and MH. Due consideration of CIMCs will help to avoid missed opportunities to integrate MH into sexual and reproductive health and vice versa. Moving forward, CIMCs need to be addressed to improve the health and well-being of women, girls, and other people who menstruate and use contraceptives globally.</p>
        </sec>
        <sec>
            <title>Data availability</title>
            <p>No data are associated with this article.</p>
        </sec>
    </body>
    <back>
        <fn-group>
            <fn>
                <p id="FN1">
                    <sup>a</sup> The terminology used to describe the needs of people who menstruate continues to evolve. Throughout this paper, &#x201c;menstrual health&#x201d; or &#x201c;MH&#x201d; will be used and is meant to encompass a comprehensive set of menstrual needs encountered through the life course as defined by Hennegan 
                    <italic toggle="yes">et al</italic>.,
                    <sup>
                        <xref ref-type="bibr" rid="ref-9">9</xref>
                    </sup>
                </p>
                <p id="FN2">
                    <sup>b</sup> In this document, menstrual and gynecologic disorders and symptoms include dysmenorrhea, heavy menstrual bleeding (or menorrhagia), endometriosis, adenomyosis, uterine leiomyomas (or fibroids), uterine polyps, polycystic ovarian syndrome (PCOS), premenstrual syndrome (PMS), and premenstrual dysphoric disorder (PMDD).</p>
                <p id="FN3">
                    <sup>c</sup> MH services include provision of menstrual materials such as pads, tampon, cups, cloth, underwear, and soap; comprehensive MH education and information; access to pain medicine and treatment for menstrual and gynecologic disorders and symptoms; and access to safe, private, accessible WASH facilities
                    <sup>
                        <xref ref-type="bibr" rid="ref-9">9</xref>
                    </sup>.</p>
            </fn>
        </fn-group>
        <ack>
            <title>Acknowledgements</title>
            <p>We appreciate all those who contributed to the CIMC Technical Consultation in November 2020, especially those who participated in the discussion groups that were used to inform the first draft of the CIMC RLA. We acknowledge the contributions of the experts who provided feedback on the CIMC RLA during the community review process. Finally, we appreciate Dr. Barbara Sow of FHI 360 for reviewing the manuscript.</p>
        </ack>
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    <sub-article article-type="reviewer-report" id="report31980">
        <front-stub>
            <article-id pub-id-type="doi">10.21956/gatesopenres.14882.r31980</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Edelman</surname>
                        <given-names>Alison</given-names>
                    </name>
                    <xref ref-type="aff" rid="r31980a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r31980a1">
                    <label>1</label>Department of Obstetrics and Gynecology, School of Medicine, Oregon Health Science University, Portland, OR, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>I was one of the researchers that participated in part of this process that the authors are reporting on. I confirm that this potential conflict of interest did not affect my ability to write an objective and unbiased review of the article.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>17</day>
                <month>5</month>
                <year>2022</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Edelman A</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport31980" related-article-type="peer-reviewed-article" xlink:href="10.12688/gatesopenres.13609.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This publication outlines the existing research, research gaps, and strategic planning processes around outcomes, terminology, and future research in the arena of contraceptive-induced menstrual changes. CMIC research needs core outcomes and an updated shared agenda in order to ensure studies both report on clinically relevant outcomes, and meta-analyses can be performed to give more robust health evidence which may result in a definite answer or again, help to better identify the next research steps. The inclusion of patient input regarding these outcomes is also essential to ensuring the research addresses the need of the end user.</p>
            <p> </p>
            <p> This paper describes the process of how to get there and provides an organized path forward.</p>
            <p> As a frequent peer reviewer, I can honestly say it was a pleasure reading this manuscript &#x2013; it was easy to read, well-written and thoughtful. It will add significantly to the literature and it will be an incredibly useful reference for those in the field. I have no minor or major edits.</p>
            <p>Does the article adequately reference differing views and opinions?</p>
            <p>Yes</p>
            <p>Are all factual statements correct, and are statements and arguments made adequately supported by citations?</p>
            <p>Yes</p>
            <p>Is the Open Letter written in accessible language?</p>
            <p>Yes</p>
            <p>Where applicable, are recommendations and next steps explained clearly for others to follow?</p>
            <p>Yes</p>
            <p>Is the rationale for the Open Letter provided in sufficient detail?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Routine and complex family planning, contraceptive induced menstrual changes, menstrual health, emergency and post-coital contraception, contraceptive development, contraceptive pharmacodynamics</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report31981">
        <front-stub>
            <article-id pub-id-type="doi">10.21956/gatesopenres.14882.r31981</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Gichangi</surname>
                        <given-names>Peter Bundi</given-names>
                    </name>
                    <xref ref-type="aff" rid="r31981a1">1</xref>
                    <xref ref-type="aff" rid="r31981a2">2</xref>
                    <xref ref-type="aff" rid="r31981a3">3</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-9636-165X</uri>
                </contrib>
                <aff id="r31981a1">
                    <label>1</label>Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium</aff>
                <aff id="r31981a2">
                    <label>2</label>Technical University of Mombasa, Mombasa, Kenya</aff>
                <aff id="r31981a3">
                    <label>3</label>International Centre for Reproductive Health-Kenya, Nairobi, Kenya</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>16</day>
                <month>5</month>
                <year>2022</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2022 Gichangi PB</copyright-statement>
                <copyright-year>2022</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport31981" related-article-type="peer-reviewed-article" xlink:href="10.12688/gatesopenres.13609.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>The topic being addressed is quite important with significant impact on the health of the individuals as well as uptake and discontinuation of family planning/contraceptives (FP/C). This is a topic which has not been addressed adequately in literature.</p>
            <p> </p>
            <p> The framework proposed to ensure there is research which is guided by identified research questions is likely to result in coherent research output.</p>
            <p> </p>
            <p> The question I am not sure is addressed adequately is the role of comprehensive counselling as measured using method plus index in Performance&#x00a0;Monitoring for Action (PMA) or DHS. This should be considered.</p>
            <p>Does the article adequately reference differing views and opinions?</p>
            <p>Yes</p>
            <p>Are all factual statements correct, and are statements and arguments made adequately supported by citations?</p>
            <p>Yes</p>
            <p>Is the Open Letter written in accessible language?</p>
            <p>Yes</p>
            <p>Where applicable, are recommendations and next steps explained clearly for others to follow?</p>
            <p>Yes</p>
            <p>Is the rationale for the Open Letter provided in sufficient detail?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Sexual and Reproductive Health, Family Planning, gender based violence, cervical cancer.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.</p>
        </body>
    </sub-article>
</article>
