NIH Public Access

Author Manuscript
Climacteric. Author manuscript; available in PMC 2013 April 01.
Published in final edited form as:
NIH-PA Author Manuscript

Climacteric. 2012 April ; 15(2): 105–114. doi:10.3109/13697137.2011.650656.

Correspondence Siobán D. Harlow, Department of Epidemiology, University of Michigan 1415 Washington Heights, Ann Arbor MI
48109. 734-763-5173, harlow@umich.edu.
STRAW+10 Program Committee
Siobán D. Harlow, PhD, Program Chair, Professor, Department of Epidemiology, University of Michigan
Margery Gass, MD, NCMP, Executive Director, The North American Menopause Society
Janet E. Hall, MD, President, The Endocrine Society; Professor, Department of Medicine, Harvard Medical School
Roger Lobo MD, President, American Society of Reproductive Medicine, Professor, Department of Obstetrics and Gynecology,
Columbia University
Pauline Maki, PhD, Professor, Departments of Psychiatry and Psychology, University of Illinois
Robert W. Rebar, MD, Executive Director, American Society for Reproductive Medicine
Sherry Sherman, PhD National Institute of Aging
Tobie J. de Villiers, MBChB, FRCOG, FCOG(SA), President, International Menopause
Society (South Africa);
STRAW+10 Invited Speakers
Valerie L. Baker, MD, Stanford University
Frank J. Broekmans, MD, PhD, University Medical Center Utrecht (Netherlands)
NIH-PA Author Manuscript

Marcelle I. Cedars, MD, University of California at San Francisco

Sybil Crawford, PhD, University of Massachusetts;
Lorraine Dennerstein, MD, University of Melbourne (Australia)
Ruth Greenblatt, MD, University of California
Georgina Hale, MD, PhD, University of Sydney (Australia)
Karl R. Hansen, MD, PhD, University of Oklahoma
Rod Little, PhD, University of Michigan
Roger Lobo, MD, Columbia University
Kathleen O’Connor, PhD, University of Washington
John F. Randolph, MD, University of Michigan
Robert Rebar, MD, American Society for Reproductive Medicine
Gloria Richard-Davis, MD, Meharry Medical College
David M. Robertson PhD, Prince Henry’s Institute of Medical Research, Monash University (Australia)
Mary Sammel, ScD, University of Pennsylvania
Claudio N. Soares, MD, PhD McMaster University
H. Irene Su, MD., University of California at San Diego
Josefina Romaguera, MD, MPH, University of Puerto Rico
Nancy Fugate Woods, RN, PhD, University of Washington
Wulf Utian, MD, Case Western Reserve School of Medicine
STRAW+10 Invited Discussants
Susan E. Appt, DVM, Wake Forest School of Medicine
Ellen W. Freeman, PhD, University of Pennsylvania
Nicole Jaff, PhD, Research Fellow, University of the Witwatersrand (South Africa)
Hadine Joffe, MD MSc, Massachusetts General Hospital
NIH-PA Author Manuscript

Jan Shifren, MD, Massachusetts General Hospital

Lynnette L. Sievert, PhD, University of Massachusetts
Patrick M. Sluss, PhD, Massachusetts General Hospital
Michelle Warren, MD, Columbia University
Junior Investigator Travel Award Recipients
Pangaja Paramsothy, MPH, University of Michigan
Miriam T. Weber, PhD, University of Rochester
Melissa F. Wellons, MD, University of Alabama
Heidi VandenBrink, University of Saskatchewan
STRAW+10 In Memoriam: MaryFran Sowers, PhD, University of Michigan
This article is being simultaneously published in the journals Climacteric, Fertility and Sterility, the Journal of Clinical Endocrinology
and Metabolism, and Menopause
DISCLOSURES MG, RR, SS declare no conflict of interest. SDH has grant support from NIA and NICHD and receives travel
support from the NAMS. JH has grant support from NIA and receives travel support from the Endocrine Society. RL is past president
of ASRM. PM receives grant support from the NIMH, NIA, NIAID and NIDA, is a member of the Board of Trustees for NAMS and
has previously consulted for Noven Pharmaceuticals, received lecture fees from the Royal Ottawa Foundation for Mental Health, the
Mayo Clinic, Baycrest, and Northwestern University and received travel support from the Society for Women’s Health Research, the
International Menopause Society, Pfizer, the Australasian Pacific Menopause Society, VCU Institute for Women’s Health. PS
received travel support from The Endocrine Society. TdeV declares no direct conflict of interest as regards the submitted paper but has
in the past received consultancy fees from Adcock Ingram and Pfizer, speaker’s fees from Servier and travel assistance to meetings
from Amgen ,Pfizer and Bayer.
 Harlow et al. Page 2

EXECUTIVE SUMMARY of STRAW+10: Addressing the

NIH-PA Author Manuscript

Unfinished Agenda of Staging Reproductive Aging

Siobán D. Harlow, PhD [Professor],
Department of Epidemiology, University of Michigan
Margery Gass, MD, NCMP [Executive Director],
The North American Menopause Society
Janet E. Hall, MD [President] [Professor],
The Endocrine Society
Department of Medicine, Harvard Medical School
Roger Lobo, MD [Professor],
Department of Obstetrics and Gynecology, Columbia University
Pauline Maki, PhD [Professor],
Department of Psychiatry and Psychology, University of Illinois
Robert W. Rebar, MD [Executive Director],
NIH-PA Author Manuscript

American Society for Reproductive Medicine

Sherry Sherman, PhD,
National Institute of Aging
Patrick M. Sluss, PhD [Associate Professor], and
Department of Pathology, Harvard Medical School
Tobie J. de Villiers, MBChB, FRCOG, FCOG (SA) [President]
International Menopause Society

Abstract
Objective—To summarize recommended updates to the 2001 Stages of Reproductive Aging
Workshop (STRAW) criteria. The 2011 STRAW+10 workshop reviewed advances in
understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before
and after the final menstrual period (FMP).
Methods—Scientists from five countries and multiple disciplines evaluated data from cohort
studies of midlife women and in the context of chronic illness and endocrine disorders, on change
NIH-PA Author Manuscript

in menstrual, endocrine and ovarian markers of reproductive aging including anti-mullerian

hormone (AMH), inhibin B, follicle-stimulating hormone (FSH), and antral follicle count (AFC).
Modifications were adopted by consensus.
Results—STRAW+10 simplified bleeding criteria for the early and late menopausal transition,
recommended modifications to criteria for the late reproductive stage (Stage − 3) and the early
post-menopause stage (Stage +1), provided information on the duration of the late transition
(Stage −1) and early post-menopause (Stage +1) and recommended application regardless of
women’s age, ethnicity, body size or lifestyle characteristics.
Conclusion—STRAW+10 provides a more comprehensive basis for assessing reproductive
aging in research and clinical contexts. Application of the STRAW+10 staging system should
improve comparability of studies of midlife women and facilitate clinical decision-making.
Nonetheless, important knowledge gaps persist and seven research priorities are identified.

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 3

Keywords
reproductive aging; ovarian aging; menopause; follicle-stimulating hormone; anti-mullerian
NIH-PA Author Manuscript

hormone; antral follicle count, inhibin B

The 2001 Stages of Reproductive Aging Workshop (STRAW) proposed nomenclature and a
staging system for ovarian aging including menstrual and qualitative hormonal criteria to
define each stage.1-4 The STRAW criteria are widely considered the gold standard for
characterizing reproductive aging through menopause, just as the Marshall-Tanner Stages
characterize pubertal maturation5. Research conducted over the past ten years has advanced
knowledge of the critical changes in hypothalamic-pituitary and ovarian function that occur
before and after the final menstrual period. These advances were the topic of a follow-up
workshop STRAW+10: Addressing the Unfinished Agenda of Staging Reproductive Aging
(STRAW+10). STRAW+10, held in Washington DC on September 20 and 21, 2011,
reviewed these scientific advances and updated the STRAW model. The sponsors were the
National Institutes of Health National Institute of Aging (NIA) and Office of Research on
Women’s Health (ORWH), the North American Menopause Society (NAMS), the American
Society for Reproductive Medicine (ASRM), the International Menopause Society (IMS)
and The Endocrine Society. The STRAW+10 workshop achieved the following aims:
1. To re-evaluate criteria for the onset of late reproductive life and the early
NIH-PA Author Manuscript

menopause given new population-based data relating to follicle-stimulating

hormone (FSH), antral follicle count (AFC), anti-mullerian hormone (AMH) and
inhibin-B;
2. To re-evaluate criteria for staging the postmenopause given new population based
data on FSH and estradiol trajectories following the final menstrual period (FMP);
3. To re-evaluate exclusion of women based on body size, lifestyle characteristics and
health status; and,
4. 4. To identify remaining gaps in scientific knowledge and research priorities.

Background and Significance

The menopausal transition marks a period of physiologic changes as women approach
reproductive senescence. Evidence supports the clinical importance of the transition for
many women as a period of temporal changes in health and quality of life (i.e., vasomotor
symptoms, sleep disturbance, depression) and longer term changes in several health
outcomes (i.e., urogenital symptoms, bone, lipids)6-15, that may influence women’s quality
of life and likelihood of healthy aging. As a standardized staging system for reproductive
NIH-PA Author Manuscript

aging, STRAW made a substantial contribution to women’s health research by providing

consistent classification of menopausal status for studies of midlife women. Importantly,
STRAW facilitated research aimed at distinguishing health effects of ovarian versus somatic
aging. STRAW criteria also serve as a clinical tool for women and their health care
providers to guide assessment of fertility, contraceptive needs and healthcare decision-
making.16, 17

Building upon prior consensus meetings of the World Health Organization and the Council
of Affiliated Menopause Societies18, STRAW re-evaluated nomenclature, proposed a
standardized staging system and recommended criteria for defining onset of each stage.
STRAW participants evaluated potential criteria including menstrual cycles, endocrinologic
parameters including FSH, estradiol, AMH, and Inhibin-B, symptoms, fertility, and ovarian
imaging including AFC. Of the candidate biomarkers considered in 2001, only FSH was
consistently measurable in a clinical setting. Data were insufficient to define quantitative

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 4

criteria for FSH or to clarify the precise timing of change in FSH trajectories. Information
on AFC and on the relationship between AMH, inhibin B and the timing of ovarian aging
was limited. Symptoms were acknowledged to be subjective and not universally
NIH-PA Author Manuscript

experienced. STRAW therefore restricted staging recommendations to menstrual cycle

bleeding criteria and qualitative FSH criteria.

Seven Stages of STRAW

STRAW divided the adult female life into 3 broad phases: reproductive, menopausal
transition, and postmenopause. These 3 phases included a total of 7 stages centered around
the final menstrual period (FMP, Stage 0).1-4 The reproductive phase was divided into Stage
−5, −4 and −3 corresponding to early, peak and late, respectively. The menopausal transition
phase consisted of Stage −2 (early) and Stage −1 (late), and the postmenopause phase
contained Stage +1 (early) and +2 (late). Stage −3 was characterized by regular menstrual
cycles and increasing levels of FSH. Stage −2 was characterized by variability in menstrual
cycle length and increased levels of FSH. Stage −1 was characterized by onset of skipped
cycles or amenorrhea of at least 60 days and continued elevation of FSH.

The ReSTAGE Collaboration subsequently conducted empirical analyses to assess the

validity and reliability of STRAW’s menstrual cycle criteria in four cohort studies – the
TREMIN study, the Melbourne Women’s Midlife Health Project (MWMHP), the Seattle
Midlife Women’s Health Study (SMWHS) and the Study of Women’s Health Across the
NIH-PA Author Manuscript

Nation (SWAN). Findings supported STRAW’s recommendations, provided more precise

specification of menstrual criteria for early and late transition and recommended a
quantitative cutpoint for FSH levels characteristic of the late transition19-23.

Generalizability
A limitation of the original STRAW was its recommendation, based on the available
evidence, that the criteria only be applied to healthy women. STRAW explicitly
recommended against applying the criteria to 7 subgroups of women1-4, including smokers
(19% of US women aged 45-6424), women with a body mass index (BMI) >30 kg/m2 (38%
of US women25) and women who had undergone hysterectomy (35% of US women26).
Women engaged in heavy aerobic exercise and women with chronic menstrual cycle
irregularities, uterine abnormalities or ovarian abnormalities were also excluded. Another
limitation of STRAW was lack of insight regarding staging in diverse populations. In 2001
few data were available from studies of multi-ethnic or diverse socio-economic populations.
Recent data from multi-ethnic cohorts now permit assessment of generalizability17, 22, 27-34,
although data from low resource countries remain quite limited.35, 36
NIH-PA Author Manuscript

STRAW had a sustained influence on research in the field, prompting assessment of

trajectories of change in endocrine levels and biomarkers of ovarian senescence as well as
evaluation of how these trajectories vary by body size, smoking, ethnicity and other
factors27-34, 37-53. Ten years later, understanding of ovarian aging and its endocrine and
clinical correlates has advanced considerably, providing a more nuanced understanding of
the critical junctures that occur during reproductive aging before and after the final
menstrual period (FMP). The role of AMH and inhibin B as markers of fertility decline and
ovarian aging is more clearly understood as are the relationships among patterns of decline
in AMH, inhibin B, AFC and primordial follicle counts27, 41, 42, 44-46, 49, 51, 54-59. The goal
of STRAW+10 was to review significant advances in the field and develop
recommendations for updating the original STRAW criteria.

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 5

Methods
STRAW+10 involved a 2-day, in-person meeting hosted at the 2011 Annual Meeting of
NIH-PA Author Manuscript

NAMS. On the first day, international experts gave oral presentations reviewing recent data
bearing on the goals, as part of a public symposium, followed by comments and discussion
from the audience. The first two sessions focused on data from prospective cohort studies of
midlife women, clinical findings related to trajectories of change in menstrual, endocrine
and ovarian markers of reproductive aging, and data relevant to how these trajectories vary
by ethnicity, body size, and smoking status. A particular focus was on patterns of change in
AMH, inhibin B, FSH, estradiol and AFC and their inter-relationships. A third session
focused on emerging evidence related to staging reproductive aging in the context of cancer
treatment, chronic illness including cancer and HIV-AIDS, and endocrine disorders
including polycystic ovarian syndrome (PCOS) and primary ovarian insufficiency (POI,
otherwise known as premature ovarian failure). At the end of day one, a panel reviewed and
participants discussed modifications that had been proposed by symposium speakers.
STRAW+10 explicitly considered feasibility of applying criteria in low resource countries.

Subsequently, 41 invited scientists convened to develop consensus and propose

modifications to the STRAW model. These participants had clinical and/or research
experience in female reproductive aging and included scientists from several key research
groups in the United States, Canada, Australia, the Netherlands and South Africa,
NIH-PA Author Manuscript

representatives from the NIH funded cohort studies of midlife women that have biological
samples60 including SWAN, the Michigan Bone Health and Metabolism Study (MBHMS),
SMWHS, Biodemographic Models of Reproductive Aging (BIMORA), and the Penn
Ovarian Aging Study (POAS) as well as the Australian MWMHP, as well as junior
investigators who submitted qualifying posters.

Three breakout groups were formed based on scientific expertise and interest. Group 1
reviewed criteria for STRAW Stages −4 to −2. Group 2 reviewed criteria for STRAW
Stages −1 to +2. Each of these two groups was subdivided into two subgroups and assigned
a rapporteur. Each subgroup proposed modifications to the STRAW paradigm separately,
considering criteria for the relevant stages in healthy women and the weight of evidence
concerning the appropriateness of applying these criteria to smokers and women regardless
of body size. Each subgroup of Group 1 and of Group 2 then reviewed the recommendations
of their paired subgroup and discussed points of disagreement until consensus was reached.
Group 3 discussed staging in the context of endocrine disorders and chronic illness and
proposed modifications. This group then integrated with one of the Group 1 or Group 2
subgroups.
NIH-PA Author Manuscript

On the second day, the 41 scientists convened to review and discuss proposed modifications.
First, Group 1 and Group 2 reviewed the other group’s recommendations proposed on the
previous day. In this way, all groups reviewed all stages under consideration (Stages −4 to
+2) Then, the group at-large met to discuss each proposal and final recommendations were
adopted by consensus. Preliminary recommendations of the STRAW+10 Workshop were
presented at the NAMS annual meeting on September 22 with comments and requests for
clarification considered by the STRAW+10 program committee.

Results
STRAW+10 retained the criteria for an ideal staging system employed by the 2001
Workshop. Thus a staging system should:
1. Rely on objective data;

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 6

2. Use widely available, reliable, noninvasive and inexpensive tests;

3. Allow for prospective classification of women; and
NIH-PA Author Manuscript

4. Permit unambiguous classification of women into a unique stage.

In addition, it was concluded that the modified staging system should:
5. Retain widely accepted nomenclature
6. Consider menstrual cycle criteria to be paramount given continuing lack of
international standardization of biomarker assays as well as their cost and/or
invasiveness, particularly in the context of resource poor countries
7. Consider biomarkers only as supportive criteria given the lack of standardization.
Supportive criteria are to be used only as necessary and should not be interpreted as
required for diagnosis.
8. Use criteria that are independent of age, symptoms and pathology. As no universal
menopausal syndrome has been established across ethnic groups61, two key symptoms
are incorporated only as descriptive additional information that may be supportive62.
The revised STRAW+10 Staging System is presented in Figure 1. STRAW+10
recommended acceptance of the ReSTAGE Collaboration’s more precise and simplified
specification of the menstrual cycle criteria for the early and late menopausal transition and
NIH-PA Author Manuscript

concurred with ReSTAGE recommendations that quantification of the FSH criteria in

STAGE −1 is possible given improved standardization of this assay. In addition, STRAW
+10 recommended modifications to criteria for the late reproductive stage (Stage −3) as well
as the early post-menopause stage (Stage +1) and provided information on the duration of
the late transition (Stage −1) and early post-menopause (Stage +1) stages. Although
additional biomarkers, especially AMH and AFC, have considerable promise, lack of
standardized assays and data from non-infertility populations remain important limitations to
their incorporation into a staging model and their utility as a clinical tool for staging
reproductive aging. Nonetheless, the revised STRAW+10 Staging System includes
qualitative criteria for these biomarkers during late reproductive life when relative changes
in these parameters have important consequences for fertility potential.

The definition and rationale for key revisions to the staging criteria include: LATE
REPRODUCTIVE STAGE (Stage −3). The late reproductive stage marks the time when
fecundability begins to decline and during which a woman may begin to notice changes in
her menstrual cycles. Given that critical endocrine parameters begin to change prior to overt
changes in menstrual cyclicity and that these endocrine changes are important to fertility
assessments, STRAW+10 recommended that the late reproductive stage be subdivided into
NIH-PA Author Manuscript

two substages (−3b and −3a). In Stage −3b, menstrual cycles remain regular without change
in length and FSH, in the context of a simultaneously measured estradiol level, remains
normal ; however, AMH and antral follicle counts are low. Most51, 63 but not all64 studies
suggest inhibin B is also low. In Stage −3a, subtle changes in menstrual cycle
characteristics, specifically shorter cycles65, 66, begin. Early follicular phase (cycle days 2-5)
FSH increases above normal, with the other three markers of ovarian aging being low.

EARLY MENOPAUSAL TRANSITION (Stage-2)

The early menopausal transition is marked by increased variability in menstrual cycle
length, defined as a persistent difference of ≤7 days in the length of consecutive cycles.
Persistence is defined as recurrence within 10 cycles of the first variable length cycle.
Cycles in the early menopausal transition are also characterized by elevated, but variable,
early follicular phase FSH levels and low AMH levels and AFC.

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 7

LATE MENOPAUSAL TRANSITION (Stage −1)

The late menopausal transition is marked by the occurrence of amenorrhea of 60 days or
NIH-PA Author Manuscript

longer. Menstrual cycles in the late menopausal transition are characterized by variability in
cycle length, extreme fluctuations in hormonal levels, and frequent anovulation. In this
stage, FSH levels are sometimes elevated into the menopausal range and sometimes within
the range characteristic of the earlier reproductive years, particularly in association with high
estradiol levels. AMH falls to undetectable levels. Development of international standards
and availability of substantive population based data now permit definition of quantitative
FSH criteria, with levels > 25 IU/L characteristic of being in late transition, based on current
international pituitary standards.67-69 Empirical analyses should be undertaken to confirm
this recommendation, and researchers and clinicians should carefully evaluate the
appropriate FSH value depending on the assay they use. Based on studies of menstrual
calendars and on changes in FSH and estradiol, this stage is estimated to last on average 1-3
years. Symptoms, most notably vasomotor symptoms, are likely to occur during this stage.

EARLY POSTMENOPAUSE (Stage +1a, +1b, +1c)

New data on the trajectories of change in mean levels of FSH and
estradiol22, 31, 33, 39, 40, 50, 52, 53 indicate that FSH continues to increase and estradiol
continues to decrease until approximately two years after the FMP, after which levels of
NIH-PA Author Manuscript

each of these hormones stabilize. Thus, STRAW +10 recommended that the Early Post-
Menopause be subdivided into 3 substages (+1a, +1b and +1c).

Stages +1a and +1b each last one year and end at the time point at which FSH and estradiol
levels stabilize. Stage +1a marks the end of the 12 month period of amenorrhea required to
define that the FMP has occurred. It corresponds to the end of the “perimenopause”, a term
still in common usage that means the time around the menopause and begins at Stage −2 and
ends 12 months after the FMP. Stage +1b includes the remainder of the period of rapid
changes in mean FSH and estradiol levels. Based on studies of hormonal changes, Stage +1a
and +1b together are estimated to last on average 2 years. Symptoms, most notably
vasomotor symptoms, are most likely to occur during this stage.

Stage +1c represents the period of stabilization of high FSH levels and low estradiol values
that is estimated to last 3 to 6 years, thus the entire early post-menopause lasts
approximately 5-8 years. Further specification of this stage will require additional studies of
trajectories of change in FSH and estradiol from the FMP through the late post-menopause.

LATE POSTMENOPAUSE (Stage +2)

NIH-PA Author Manuscript

Stage +2 represents the period in which further changes in reproductive endocrine function
are more limited and processes of somatic aging become of paramount concern. Symptoms
of vaginal dryness and urogenital atrophy become increasingly prevalent at this time.
However, mean FSH levels fall again many years after menopause in the very elderly70;
future studies are needed to determine if an additional stage near the end of life is warranted.

INCLUSIVENESS OF THE STRAW+10 CRITERIA

Evidence now supports the applicability of the STRAW+10 recommendations for the
majority of women. Epidemiologic and clinical studies have documented that the process of
reproductive aging, although influenced by demographic factors, lifestyle and BMI, follows
a robust and predictable pattern.22, 27, 28, 33, 34, 40, 71 While smoking and BMI influence
hormonal levels and the timing of transition, these factors do not alter the trajectory of
change in bleeding patterns or hormonal levels with reproductive aging. Thus the STRAW

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 8

+10 staging system is applicable to women regardless of age, demographic, BMI or lifestyle
characteristics.
NIH-PA Author Manuscript

The STRAW+10 model does not use age as a criteria for determining reproductive staging.
However, women meeting the criteria for Primary Ovarian Insufficiency/Premature Ovarian
Failure (POI/POA; age < 40 with 4 months of amenorrhea and 2 serum FSH levels [at least a
month apart] in the menopausal range) may not easily fit into this model. The course of
reproductive aging in women with POI/POA may be considerably more variable than that of
normal reproductive aging. Not only are there several potential etiologies but a substantial
proportion of women have spontaneous resumption of menstrual function even once the
diagnosis has been confirmed.72. Additional research is needed to better document the
process of ovarian aging in these women and whether the course of ovarian aging differs by
etiology of POI. Studies of reproductive aging in POI are considered to be a research
priority.

HYSTERECTOMY AND ENDOMETRIAL ABLATION

Women who have undergone hysterectomy or endometrial ablation cannot be staged by
menstrual bleeding criteria73. Reproductive stage in these women can only be assessed by
the supportive criteria of biomarkers of ovarian aging. It is recommended that clinicians and
researchers wait at least 3 months post surgery to assess endocrine status given emerging
evidence that pelvic surgeries may transiently raise FSH levels74-77. Further research on the
NIH-PA Author Manuscript

nature and duration of alterations in biomarkers of ovarian aging secondary to pelvic surgery
is warranted. In most cases, staging will be limited to classification of whether such women
are premenopausal or postmenopausal. A single sample for measurement of FSH and
estradiol may be ambiguous or misleading, and a repeated measurement is often required.

POLYCYSTIC OVARIAN SYNDROME (PCOS)

Women with PCOS frequently experience oligomenorrhea that is not attributable to ovarian
aging. Thus, the current menstrual cycle criteria used to stage reproductive aging are not
applicable to this population. Understanding of the changes occurring prior to menopause in
this group of women is limited. Some data suggest that women with PCOS may experience
a later age at menopause56, 78, however, the experience of reproductive aging in PCOS is not
well understood. Similarly, menstrual cycle criteria are not applicable in women with
hypothalamic amenorrhea. Studies of reproductive aging in these subgroups of women are
considered to be a research priority.

WOMEN WITH CHRONIC ILLNESS AND UNDERGOING CHEMOTHERAPY

NIH-PA Author Manuscript

Several important subgroups remain difficult to stage yet deserve attention in any staging
system.57, 79-82 Depending on age at treatment and cancer treatment type, a significant
proportion of women who undergo cancer treatment, particularly with alkylating agents,
may experience transient increases in FSH and decreases in AMH and AFC with return of
bleeding even after 12 months or more of amenorrhea.57, 81-83 In these patients, resumption
of menstrual cycles may not indicate return of normal menstrual function. Women
undergoing treatment with tamoxifen pose an additional problem as FSH and estradiol levels
may be altered by this treatment which can also cause abnormal bleeding through direct
effects on the endometrium. Women with chronic illnesses such HIV/AIDS also pose a
problem in staging of reproductive aging due to lack of reliability of bleeding patterns and
hormonal markers.79, 80 Staging in these women will require assessment with menstrual
cycle criteria, the supportive criteria using relevant biomarkers, and age, to better
characterize their ovarian function. Large prospective cohort studies are needed to better
characterize the trajectories of ovarian aging in these populations.

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 9

CONCLUSION AND RESEARCH PRIORITIES

STRAW+10 revised and extended the STRAW recommendations to include additional
NIH-PA Author Manuscript

criteria for defining specific stages of reproductive life. The revised staging system provides
a more comprehensive basis for classification and assessment from the late reproductive
stage through the menopausal transition and into the postmenopause. Its application should
improve comparability of studies of midlife women by establishing clear criteria for
ascertaining women’s reproductive stage. The STRAW+10 recommendations are expected
to improve guidance for classifying the ovarian status of midlife women in the research
setting while advancing efforts to translate this new science for clinicians and women.

Although scientific understanding of ovarian aging has advanced considerably in the last
decade, important gaps in scientific knowledge persist. The workshop participants identified
seven research priorities.
1. Lack of standardized assays for key biomarkers remains an important limitation in
efforts to stage reproductive aging and to translate research findings to cost-
effective clinical tools. Given the importance of AMH in relation to fertility and its
relative stability across the menstrual cycle, development of an international
standard for assessment of AMH is of paramount importance.
2. Empirical analysis across multiple cohorts is needed to specify precise menstrual
NIH-PA Author Manuscript

cycle criteria for Stages −3b and −3a.

3. Studies are needed to characterize the hormonal changes of the postmenopause
from Stage +1 to +2 as data across these stages are limited; several cohort studies
are well positioned to provide this information.
4. Given that the large cohort studies of midlife women were initiated before the
STRAW staging system was developed, these cohorts should be supported to apply
the STRAW+10 staging criteria in order to reanalyze key findings on the clinical
changes that occur across the menopausal transition.
5. Improved characterization of the pattern, timing, and level of reproductive
biomarkers across nations is necessary, especially to provide data on the experience
of women from low resource countries.
6. Research is needed to better understand the process of reproductive aging and
appropriate staging criteria for women with PCOS and POI, and when removal of a
single ovary and/or hysterectomy has occurred.
7. Research is needed to better evaluate staging in women with chronic illness such as
HIV and those undergoing cancer treatment.
NIH-PA Author Manuscript

Acknowledgments
The STRAW+10 workshop had grant support from the National Institutes of Health (NIH), DHHS, through the
National Institute on Aging (NIA) (AG039961) and the NIH Office of Research on Women’s Health (ORWH) as
well as from the North American Menopause Society (NAMS), the American Society for Reproductive Medicine
(ASRM), the International Menopause Society (IMS) and the Endocrine Society. This paper is solely the
responsibility of the authors and does not necessarily represent the official views of the NIA, ORWH or the NIH.

References
1. Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging
Workshop (STRAW). Climacteric. 2001; 4(4):267–72. [PubMed: 11770182]
2. Soules MR, Sherman S, Parrott E, et al. Stages of Reproductive Aging Workshop (STRAW). J
Womens Health Gend Based Med. 2001; 10(9):843–8. [PubMed: 11747678]

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 10

3. Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging
Workshop (STRAW). Fertil Steril. 2001; 76(5):874–8. [PubMed: 11704104]
4. Soules MR, Sherman S, Parrott E, et al. Executive summary: Stages of Reproductive Aging
NIH-PA Author Manuscript

Workshop (STRAW) Park City, Utah, July, 2001. Menopause. 2001; 8(6):402–7. [PubMed:
21141649]
5. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;
44(235):291–303. [PubMed: 5785179]
6. Bromberger JT, Schott LL, Kravitz HM, et al. Longitudinal change in reproductive hormones and
depressive symptoms across the menopausal transition: results from the Study of Women’s Health
Across the Nation (SWAN). Arch Gen Psychiatry. 2010; 67(6):598–607. [PubMed: 20530009]
7. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based
study of menopausal symptoms. Obstet Gynecol. 2000; 96(3):351–8. [PubMed: 10960625]
8. Freeman EW, Grisso JA, Berlin J, Sammel M, Garcia-Espana B, Hollander L. Symptom reports
from a cohort of African American and white women in the late reproductive years. Menopause.
2001; 8(1):33–42. [PubMed: 11201513]
9. Hollander LE, Freeman EW, Sammel MD, Berlin JA, Grisso JA, Battistini M. Sleep quality,
estradiol levels, and behavioral factors in late reproductive age women. Obstet Gynecol. 2001;
98(3):391–7. [PubMed: 11530118]
10. Lee CG, Carr MC, Murdoch SJ, et al. Adipokines, inflammation, and visceral adiposity across the
menopausal transition: a prospective study. J Clin Endocrinol Metab. 2009; 94(4):1104–10.
[PubMed: 19126626]
NIH-PA Author Manuscript

11. Maki PM, Freeman EW, Greendale GA, et al. Summary of the National Institute on Aging-
sponsored conference on depressive symptoms and cognitive complaints in the menopausal
transition. Menopause. 2010; 17(4):815–22. [PubMed: 20616668]
12. Matthews KA, Crawford SL, Chae CU, et al. Are changes in cardiovascular disease risk factors in
midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol.
2009; 54(25):2366–73. [PubMed: 20082925]
13. Neer RM. Bone loss across the menopausal transition. Ann N Y Acad Sci. 2010; 1192:66–71.
[PubMed: 20392219]
14. Sowers MR, Jannausch M, McConnell D, et al. Hormone predictors of bone mineral density
changes during the menopausal transition. J Clin Endocrinol Metab. 2006; 91(4):1261–7.
[PubMed: 16403818]
15. Woods NF, Mitchell ES. Sleep symptoms during the menopausal transition and early
postmenopause: observations from the Seattle Midlife Women’s Health Study. Sleep. 2010; 33(4):
539–49. [PubMed: 20394324]
16. Bastian LA, Smith CM, Nanda K. Is this woman perimenopausal? JAMA. 2003; 289(7):895–902.
[PubMed: 12588275]
17. Santoro N, Brockwell S, Johnston J, et al. Helping midlife women predict the onset of the final
menses: SWAN, the Study of Women’s Health Across the Nation. Menopause. 2007; 14(3 Pt 1):
415–24. [PubMed: 17303963]
NIH-PA Author Manuscript

18. Utian WH. Menopause-related definitions. International Congress Series. 2004; 1266:133–8.
19. Harlow SD, Cain K, Crawford S, et al. Evaluation of four proposed bleeding criteria for the onset
of late menopausal transition. J Clin Endocrinol Metab. 2006; 91(9):3432–8. [PubMed: 16772350]
20. Harlow SD, Crawford S, Dennerstein L, Burger HG, Mitchell ES, Sowers MF. Recommendations
from a multi-study evaluation of proposed criteria for staging reproductive aging. Climacteric.
2007; 10(2):112–9. [PubMed: 17453859]
21. Harlow SD, Mitchell ES, Crawford S, Nan B, Little R, Taffe J. The ReSTAGE Collaboration:
defining optimal bleeding criteria for onset of early menopausal transition. Fertil Steril. 2008;
89(1):129–40. [PubMed: 17681300]
22. Randolph JF Jr. Zheng H, Sowers MR, et al. Change in follicle-stimulating hormone and estradiol
across the menopausal transition: effect of age at the final menstrual period. J Clin Endocrinol
Metab. 2011; 96(3):746–54. [PubMed: 21159842]

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 11

23. Taffe JR, Cain KC, Mitchell ES, Woods NF, Crawford SL, Harlow SD. “Persistence” improves the
60-day amenorrhea marker of entry to late-stage menopausal transition for women aged 40 to 44
years. Menopause. 17(1):191–3. [PubMed: 19713872]
NIH-PA Author Manuscript

24. Vital signs: current cigarette smoking among adults aged >or=18 years --- United States. MMWR
Morb Mortal Wkly Rep. 2009; 59(35):1135–40.
25. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults,
1999-2008. JAMA. 2010; 303(3):235–41. [PubMed: 20071471]
26. Merrill RM, Layman AB, Oderda G, Asche C. Risk estimates of hysterectomy and selected
conditions commonly treated with hysterectomy. Ann Epidemiol. 2008; 18(3):253–60. [PubMed:
18280923]
27. Freeman EW, Gracia CR, Sammel MD, Lin H, Lim LC, Strauss JF 3rd. Association of anti-
mullerian hormone levels with obesity in late reproductive-age women. Fertil Steril. 2007; 87(1):
101–6. [PubMed: 17109858]
28. Gracia CR, Freeman EW, Sammel MD, Lin H, Nelson DB. The relationship between obesity and
race on inhibin B during the menopause transition. Menopause. 2005; 12(5):559–66. [PubMed:
16145310]
29. Huddleston HG, Cedars MI, Sohn SH, Giudice LC, Fujimoto VY. Racial and ethnic disparities in
reproductive endocrinology and infertility. Am J Obstet Gynecol. 2010; 202(5):413–9. [PubMed:
20207341]
30. Manson JM, Sammel MD, Freeman EW, Grisso JA. Racial differences in sex hormone levels in
women approaching the transition to menopause. Fertil Steril. 2001; 75(2):297–304. [PubMed:
NIH-PA Author Manuscript

11172830]
31. Randolph JF Jr. Sowers M, Bondarenko IV, Harlow SD, Luborsky JL, Little RJ. Change in
estradiol and follicle-stimulating hormone across the early menopausal transition: effects of
ethnicity and age. J Clin Endocrinol Metab. 2004; 89(4):1555–61. [PubMed: 15070912]
32. Randolph JF Jr. Sowers M, Gold EB, et al. Reproductive hormones in the early menopausal
transition: relationship to ethnicity, body size, and menopausal status. J Clin Endocrinol Metab.
2003; 88(4):1516–22. [PubMed: 12679432]
33. Sammel MD, Freeman EW, Liu Z, Lin H, Guo W. Factors that influence entry into stages of the
menopausal transition. Menopause. 2009; 16(6):1218–27. [PubMed: 19512950]
34. Su HI, Sammel MD, Freeman EW, Lin H, DeBlasis T, Gracia CR. Body size affects measures of
ovarian reserve in late reproductive age women. Menopause. 2008; 15(5):857–61. [PubMed:
18427357]
35. Sievert LL, Begum K, Sharmeen T, Chowdhury O, Muttukrishna S, Bentley G. Patterns of
occurrence and concordance between subjective and objective hot flashes among Muslim and
Hindu women in Sylhet, Bangladesh. Am J Hum Biol. 2008; 20(5):598–604. [PubMed: 18461600]
36. Sievert LL, Saliba M, Reher D, et al. The medical management of menopause: a four-country
comparison care in urban areas. Maturitas. 2008; 59(1):7–21. [PubMed: 18178044]
37. Battistini M, Freeman EW, Grisso JA, Sammel M, Hollander L, Garcia-Espana B. Pilot study of
racial differences and longitudinal changes in inhibin B in the late reproductive years. Fertil Steril.
NIH-PA Author Manuscript

2002; 77(1):193–5. [PubMed: 11779617]

38. Burger HG, Hale GE, Dennerstein L, Robertson DM. Cycle and hormone changes during
perimenopause: the key role of ovarian function. Menopause. 2008; 15(4 Pt 1):603–12. [PubMed:
18574431]
39. Burger HG, Hale GE, Robertson DM, Dennerstein L. A review of hormonal changes during the
menopausal transition: focus on findings from the Melbourne Women’s Midlife Health Project.
Hum Reprod Update. 2007; 13(6):559–65. [PubMed: 17630397]
40. Freeman EW, Sammel MD, Lin H, Gracia CR. Obesity and reproductive hormone levels in the
transition to menopause. Menopause. 2010; 17(4):718–26. [PubMed: 20216473]
41. Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS. Endocrine features of
menstrual cycles in middle and late reproductive age and the menopausal transition classified
according to the Staging of Reproductive Aging Workshop (STRAW) staging system. J Clin
Endocrinol Metab. 2007; 92(8):3060–7. [PubMed: 17550960]

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 12

42. Hansen KR, Hodnett GM, Knowlton N, Craig LB. Correlation of ovarian reserve tests with
histologically determined primordial follicle number. Fertil Steril. 2011; 95(1):170–5. [PubMed:
20522327]
NIH-PA Author Manuscript

43. Hansen KR, Morris JL, Thyer AC, Soules MR. Reproductive aging and variability in the ovarian
antral follicle count: application in the clinical setting. Fertil Steril. 2003; 80(3):577–83. [PubMed:
12969701]
44. Klein NA, Houmard BS, Hansen KR, et al. Age-related analysis of inhibin A, inhibin B, and
activin a relative to the intercycle monotropic follicle-stimulating hormone rise in normal
ovulatory women. J Clin Endocrinol Metab. 2004; 89(6):2977–81. [PubMed: 15181087]
45. Knauff EA, Eijkemans MJ, Lambalk CB, et al. Anti-Mullerian hormone, inhibin B, and antral
follicle count in young women with ovarian failure. J Clin Endocrinol Metab. 2009; 94(3):786–92.
[PubMed: 19066296]
46. La Marca A, Sighinolfi G, Radi D, et al. Anti-Mullerian hormone (AMH) as a predictive marker in
assisted reproductive technology (ART). Hum Reprod Update. 2010; 16(2):113–30. [PubMed:
19793843]
47. O’Connor KA, Ferrell R, Brindle E, et al. Progesterone and ovulation across stages of the
transition to menopause. Menopause. 2009; 16(6):1178–87. [PubMed: 19568209]
48. O’Connor KA, Ferrell RJ, Brindle E, et al. Total and unopposed estrogen exposure across stages of
the transition to menopause. Cancer Epidemiol Biomarkers Prev. 2009; 18(3):828–36. [PubMed:
19240232]
49. Robertson DM. Anti-Mullerian hormone as a marker of ovarian reserve: an update. Womens
NIH-PA Author Manuscript

Health (Lond Engl). 2008; 4(2):137–41. [PubMed: 19072515]

50. Robertson DM, Hale GE, Jolley D, Fraser IS, Hughes CL, Burger HG. Interrelationships between
ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age. J Clin
Endocrinol Metab. 2009; 94(1):138–44. [PubMed: 18854393]
51. Sowers MR, Eyvazzadeh AD, McConnell D, et al. Anti-mullerian hormone and inhibin B in the
definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab. 2008; 93(9):
3478–83. [PubMed: 18593767]
52. Sowers MR, Zheng H, McConnell D, Nan B, Harlow S, Randolph JF Jr. Follicle stimulating
hormone and its rate of change in defining menopause transition stages. J Clin Endocrinol Metab.
2008; 93(10):3958–64. [PubMed: 18647816]
53. Sowers MR, Zheng H, McConnell D, Nan B, Harlow SD, Randolph JF Jr. Estradiol rates of change
in relation to the final menstrual period in a population-based cohort of women. J Clin Endocrinol
Metab. 2008; 93(10):3847–52. [PubMed: 18647803]
54. Broekmans FJ, Faddy MJ, Scheffer G, te Velde ER. Antral follicle counts are related to age at
natural fertility loss and age at menopause. Menopause. 2004; 11(6 Pt 1):607–14. [PubMed:
15545788]
55. Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences.
Endocr Rev. 2009; 30(5):465–93. [PubMed: 19589949]
56. Mulders AG, Laven JS, Eijkemans MJ, de Jong FH, Themmen AP, Fauser BC. Changes in anti-
NIH-PA Author Manuscript

Mullerian hormone serum concentrations over time suggest delayed ovarian ageing in
normogonadotrophic anovulatory infertility. Hum Reprod. 2004; 19(9):2036–42. [PubMed:
15217995]
57. Su HI, Sammel MD, Green J, et al. Antimullerian hormone and inhibin B are hormone measures of
ovarian function in late reproductive-aged breast cancer survivors. Cancer. 2010; 116(3):592–9.
[PubMed: 19918920]
58. van Disseldorp J, Faddy MJ, Themmen AP, et al. Relationship of serum antimullerian hormone
concentration to age at menopause. J Clin Endocrinol Metab. 2008; 93(6):2129–34. [PubMed:
18334591]
59. van Rooij IA, Broekmans FJ, Scheffer GJ, et al. Serum antimullerian hormone levels best reflect
the reproductive decline with age in normal women with proven fertility: a longitudinal study.
Fertil Steril. 2005; 83(4):979–87. [PubMed: 15820810]
60. Ferrell RJ, Sowers M. Longitudinal, epidemiologic studies of female reproductive aging. Ann N Y
Acad Sci. 2010; 1204:188–97. [PubMed: 20738290]

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 13

61. Avis NE, Brockwell S, Randolph JF Jr. et al. Longitudinal changes in sexual functioning as women
transition through menopause: results from the Study of Women’s Health Across the Nation.
Menopause. 2009; 16(3):442–52. [PubMed: 19212271]
NIH-PA Author Manuscript

62. Avis NE, Zhao X, Johannes CB, Ory M, Brockwell S, Greendale GA. Correlates of sexual function
among multi-ethnic middle-aged women: results from the Study of Women’s Health Across the
Nation (SWAN). Menopause. 2005; 12(4):385–98. [PubMed: 16037753]
63. Welt CK, McNicholl DJ, Taylor AE, Hall JE. Female reproductive aging is marked by decreased
secretion of dimeric inhibin. J Clin Endocrinol Metab. 1999; 84(1):105–11. [PubMed: 9920069]
64. Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. A proposed classification system for
menstrual cycles in the menopause transition based on changes in serum hormone profiles.
Menopause. 2008; 15(6):1139–44. [PubMed: 18779761]
65. Johannes CB, Crawford SL, Longcope C, McKinlay SM. Bleeding patterns and changes in the
perimenopause: a longitudinal characterization of menstrual cycles. Clinical Consultations in
Obstetrics and Gyncecology. 1996; 8:9–20.
66. Mitchell ES, Woods NF, Mariella A. Three stages of the menopausal transition from the Seattle
Midlife Women’s Health Study: toward a more precise definition. Menopause. 2000; 7(5):334–49.
[PubMed: 10993033]
67. Roche Diagnostics. Package Insert: Elecsys and Cobas e analyzers. Vol. V 13. Roche Diagnostics;
Indianapolis, IN: 2006-11. FSH, Follicle Stimulating Hormone.
68. Abbott Laboratories. FSH. Package Insert: Architect Analyzers; 6C24, 34-4680/R1. 2007-10.
69. Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P. Establishment of detailed reference
NIH-PA Author Manuscript

values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during
different phases of the menstrual cycle on the Abbott ARCHITECT analyzer. Clin Chem Lab
Med. 2006; 44(7):883–7. [PubMed: 16776638]
70. Hall JE. Neuroendocrine physiology of the early and late menopause. Endocrinol Metab Clin
North Am. 2004; 33(4):637–59. [PubMed: 15501638]
71. Schmitz KH, Lin H, Sammel MD, et al. Association of physical activity with reproductive
hormones: the Penn Ovarian Aging Study. Cancer Epidemiol Biomarkers Prev. 2007; 16(10):
2042–7. [PubMed: 17905944]
72. Bidet M, Bachelot A, Bissauge E, et al. Resumption of Ovarian Function and Pregnancies in 358
Patients with Premature Ovarian Failure. J Clin Endocrinol Metab. 2011
73. Johnson BD, Merz CN, Braunstein GD, et al. Determination of menopausal status in women: the
NHLBI-sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study. J Womens Health
(Larchmt). 2004; 13(8):872–87. [PubMed: 15671703]
74. Gelbaya TA, Nardo LG, Fitzgerald CT, Horne G, Brison DR, Lieberman BA. Ovarian response to
gonadotropins after laparoscopic salpingectomy or the division of fallopian tubes for
hydrosalpinges. Fertil Steril. 2006; 85(5):1464–8. [PubMed: 16580673]
75. Hehenkamp WJ, Volkers NA, Broekmans FJ, et al. Loss of ovarian reserve after uterine artery
embolization: a randomized comparison with hysterectomy. Hum Reprod. 2007; 22(7):1996–2005.
[PubMed: 17582145]
NIH-PA Author Manuscript

76. Qu X, Cheng Z, Yang W, Xu L, Dai H, Hu L. Controlled clinical trial assessing the effect of
laparoscopic uterine arterial occlusion on ovarian reserve. J Minim Invasive Gynecol. 2010; 17(1):
47–52. [PubMed: 20129332]
77. Sezik M, Ozkaya O, Demir F, Sezik HT, Kaya H. Total salpingectomy during abdominal
hysterectomy: effects on ovarian reserve and ovarian stromal blood flow. J Obstet Gynaecol Res.
2007; 33(6):863–9. [PubMed: 18001455]
78. Dahlgren E, Johansson S, Lindstedt G, et al. Women with polycystic ovary syndrome wedge
resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating
hormones. Fertil Steril. 1992; 57(3):505–13. [PubMed: 1740195]
79. Santoro N, Arnsten JH, Buono D, Howard AA, Schoenbaum EE. Impact of street drug use, HIV
infection, and highly active antiretroviral therapy on reproductive hormones in middle-aged
women. J Womens Health (Larchmt). 2005; 14(10):898–905. [PubMed: 16372891]
80. Santoro N, Lo Y, Moskaleva G, et al. Factors affecting reproductive hormones in HIV-infected,
substance-using middle-aged women. Menopause. 2007; 14(5):859–65. [PubMed: 17415019]

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 14

81. Su, HI.; Alton, J.; Sherman, L.; Stankiewicz, C.; Ratcliffe, S.; DeMichele, A. Relationships
between clinical and biochemical predictors of chemotherapy related amenorrhea in
premenopausal adjuvant breast cancer patients. American Society of Clinical Oncology Annual
NIH-PA Author Manuscript

Meeting Proceedings; p. 11011

82. Su HI, Sammel MD, Velders L, et al. Association of cyclophosphamide drug-metabolizing enzyme
polymorphisms and chemotherapy-related ovarian failure in breast cancer survivors. Fertil Steril.
2009; 94(2):645–54. [PubMed: 19376514]
83. Sukumvanich P, Case LD, Van Zee K, et al. Incidence and time course of bleeding after long-term
amenorrhea after breast cancer treatment: a prospective study. Cancer. 2010; 116(13):3102–11.
[PubMed: 20564648]
NIH-PA Author Manuscript
NIH-PA Author Manuscript

Climacteric. Author manuscript; available in PMC 2013 April 01.

 Harlow et al. Page 15
NIH-PA Author Manuscript
NIH-PA Author Manuscript

Figure 1.
The STRAW+10 Staging System for Reproductive Aging in Women
NIH-PA Author Manuscript

Climacteric. Author manuscript; available in PMC 2013 April 01.