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Menstrual changes mark reproductive aging.


Changes to the menstrual cycle remain the most important clinical indicators of women's reproductive aging, according to new standardized staging criteria.

The changes identified by the most recent Stages of Reproductive Aging Workshop are now defined in 10 stages, whereas the 2001 STRAW criteria had 7. The new criteria, called STRAW-10, offer more detail on the characteristics of flow and cycle length at each stage, along with corresponding endocrine changes. The article was published simultaneously in Menopause, Climacteric, Fertility and Sterility, and the Journal of Clinical Endocrinology and Metabolism.


For example, the late reproductive stage is now subdivided into two stages, -3b and -3a, instead of only stage -3 as before (Menopause 2012 Feb. 16 [doi:10.1097/gme0b013c31824d8f40]). In stage -3b, flow remains regular, whereas in stage -3a there are subtle changes in flow and length of cycle.

The postmenopausal stage + 1, identified in the earlier STRAW criteria, also has been subdivided into three lettered stages, with the endocrine changes and duration of each stage described.

Unlike the previous STRAW criteria, the menstrual changes identified in STRAW-10 are relevant to any healthy woman, regardless of ethnicity, age, body mass index, or lifestyle, researchers said, noting that although factors such as smoking status and BMI may affect the timing of menopause, the bleeding patterns remain reliable indicators of the reproductive stage.

"Despite the availability of blood tests and sonograms, the menstrual cycle remains the single best way to estimate where a woman is along the reproductive path," commented Dr. Margery Gass, one of the coauthors of the new criteria, the executive director of the North American Menopause Society, and the editor of Menopause.

'According to STRAW-10, most women (and their clinicians) can use the changes in their menstrual pattern to determine how close they are to menopause: late reproductive phase (subtle changes in cycle length and blood flow), early menopause transition (menstrual period 7 or more days early or late), and late menopause transition (the occurrence of more than 60 days between cycles)," Dr. Gass said in an interview.

STRAW-10 incorporates three biomarkers--anti-Mullerian hormone (AMH), inhibin B, and antral follicle count- that are not mentioned in the original STRAW criteria, along with follicle-stimulating hormone (FSH), which was included in the original criteria.

In developing the new criteria, an international group of 41 researchers, led by epidemiologist Sioban D. Harlow, Ph.D., of the University of Michigan, Ann Arbor, evaluated data from cohort studies of midlife women with the aim to incorporate the scientific findings of the past decade on ovarian aging and its endocrine and clinical indicators.

Although much has been learned since 2001 with regard to biomarkers, Dr. Harlow and colleagues emphasized that the biomarker criteria outlined in STRAW-10 must still be considered "supportive," in part because more research is needed and in part because of the invasiveness and expense of testing.

Dr. Gass commented that for clinicians, checking hormone levels should not be considered necessary "except in women who have undergone endometrial ablation or hysterectomy, or who have unusual health circumstances."

Women for whom the STRAW-10 criteria are not applicable include those with polycystic ovarian syndrome or hypothalamic amenorrhea. Women with chronic illnesses such as HIV-AIDS, or those who are undergoing certain types of cancer treatments, also are difficult to assess under STRAW-10, as cycles and hormone levels can change in response to medication.

Although the new criteria do not use age in determining reproductive staging, women younger than 40 years who have premature ovarian insufficiency or premature ovarian failure do not fit well under STRAW10, the researchers noted, as their course of reproductive aging is more variable.

The STRAW-10 meetings received funding from the National Institutes of Health and the Department of Health and Human Services through the National Institute on Aging (NIA) and the Office of Research on Women's Health, as well as the North American Menopause Society (NAMS), the American Society for Reproductive Medicine (ASRM), the International Menopause Society in Cape Town, South Africa, and the Endocrine Society

Dr. Gass receives support from NAMS. Dr. Harlow disclosed support from the NIA and NAMS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Coauthor Dr. Janet E. Hall disclosed support from NIA and the Endocrine Society. Dr. Roger Lobo is a past president of the ASRM, and Dr. Robert W. Rebar disclosed salary support from ASRM. Pauline Maki, Ph.D., disclosed support from the NIA and other public sources along with board membership on NAMS, a consultant relationship with Noven Pharmaceuticals, and lecture fees from Pfizer and others. Dr. Tobie J. de Villiers disclosed past support from Adcock Ingram, Servier, Pfizer, Bayer, and Amgen without direct bearing on the STRAW- 10 work. The remaining two coauthors said they had no relevant financial disclosures.

Related Article: STRAW-10 changes will aid research.

The main changes [in STRAW-10] have to do with the late reproductive stage and the early postmenopausal stage, which has been subdivided to give more detail, and in turn help understand the physiologic changes which occur at these times. In particular, the late reproductive stage has been subdivided so the measurement of the anti-Mullerian hormone (AMH) and follicle count can be used as a measure of decreased fertility, but the menstrual bleeding is still regular and unchanged. Inhibin B also may be low.

The next stage adds a change in menstrual pattern, usually shorter cycles, and also some variability in FSH levels early in the cycle (days 2-5). Unfortunately, there is no standardization for the AMH assay, so a quantitative measurement is not available.

The bottom line is that these definitions will be helpful mostly for research, but will only give us some guidance to counsel patients about their fertility.

In terms of the late reproductive stages, there now are three subdivisions based on stabilization of key hormones at this time (FSH and estradiol). Perimenopause also is better defined and the addition of symptoms with a description of bleeding patterns will be helpful both to researchers and clinicians. This will lead to more research and understanding of the key physiologic events that lead to repro ductive decline and menopausal changes.

There also is a description of what happens to reproduction with various dysfunctions, such as chemotherapy and in polycystic ovarian syndrome, which can be helpful both clinically and particularly in research.

MICHELLE WARREN, M.D., is professor of medicine and obstetrics and gynecology at Columbia University Medical Center, New York, and medical director of the Center for Menopause, Hormonal Disorders, and Women's Health at Columbia. She commented in an interview regarding the STRAW- 10 findings. She disclosed ties with Pfizer, Yoplait, and Ascend Therapeutics.
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Author:Smith, Jennie
Publication:Family Practice News
Geographic Code:1USA
Date:Mar 1, 2012
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